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1. Inflammation and immune system pathways as biological signatures of adolescent depression—the IDEA-RiSCo study

Author

Valentina Zonca, Moira Marizzoni, Samantha Saleri, Zuzanna Zajkowska, Pedro H. Manfro, Laila Souza, Anna Viduani, Luca Sforzini, Johnna R. Swartz, Helen L. Fisher, Brandon A. Kohrt, Christian Kieling, Marco Andrea Riva, Annamaria Cattaneo, and Valeria Mondelli

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract The biological mechanisms underlying the onset of major depressive disorder (MDD) have predominantly been studied in adult populations from high-income countries, despite the onset of depression typically occurring in adolescence and the majority of the world’s adolescents living in low- and middle-income countries (LMIC). Taking advantage of a unique adolescent sample in an LMIC (Brazil), this study aimed to identify biological pathways characterizing the presence and increased risk of depression in adolescence, and sex-specific differences in such biological signatures. We collected blood samples from a risk-stratified cohort of 150 Brazilian adolescents (aged 14–16 years old) comprising 50 adolescents with MDD, 50 adolescents at high risk of developing MDD but without current MDD, and 50 adolescents at low risk of developing MDD and without MDD (25 females and 25 males in each group). We conducted RNA-Seq and pathway analysis on whole blood. Inflammatory-related biological pathways, such as role of hypercytokinemia/hyperchemokinemia in the pathogenesis of influenza (z-score = 3.464, p

Published
2024
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2. Vulnerability and resilience to prenatal stress exposure: behavioral and molecular characterization in adolescent rats

Author

Kerstin Camile Creutzberg, Veronica Begni, Rodrigo Orso, Francisco Sindermann Lumertz, Luis Eduardo Wearick-Silva, Saulo Gantes Tractenberg, Moira Marizzoni, Annamaria Cattaneo, Rodrigo Grassi-Oliveira, and Marco Andrea Riva

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Exposure to stress can lead to long lasting behavioral and neurobiological consequences, which may enhance the susceptibility for the onset of mental disorders. However, there are significant individual differences in the outcome of stress exposure since only a percentage of exposed individuals may show pathological consequences, whereas others appear to be resilient. In this study, we aimed to characterize the effects of prenatal stress (PNS) exposure in rats at adolescence and to identify subgroup of animals with a differential response to the gestational manipulation. PNS adolescent offspring (regardless of sex) showed impaired emotionality in different pathological domains, such as anhedonia, anxiety, and sociability. However, using cluster analysis of the behavioral data we could identify 70% of PNS-exposed animals as vulnerable (PNS-vul), whereas the remaining 30% were considered resilient (PNS-res). At the molecular level, we found that PNS-res males show a reduced basal activation of the ventral hippocampus whereas other regions, such as amygdala and dorsal hippocampus, show significant PNS-induced changes regardless from vulnerability or resilience. Taken together, our results provide evidence of the variability in the behavioral and neurobiological effects of PNS-exposed offspring at adolescence. While these data may advance our understanding of the association between exposure to stress during gestation and the risk for psychopathology, the investigation of the mechanisms associated to stress vulnerability or resilience may be instrumental to develop novel strategies for therapeutic intervention.

Published
2023
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3. Microstructural alterations in the locus coeruleus‐entorhinal cortex pathway in Alzheimer's disease and frontotemporal dementia

Author

Giulia Quattrini, Lorenzo Pini, Ilaria Boscolo Galazzo, Ileana O. Jelescu, Jorge Jovicich, Rosa Manenti, Giovanni B. Frisoni, Moira Marizzoni, Francesca B. Pizzini, and Michela Pievani

Subjects
Alzheimer's disease, behavioral variant frontotemporal dementia, diffusion tensor imaging, entorhinal cortex, locus coeruleus, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract

Abstract INTRODUCTION We investigated in vivo the microstructural integrity of the pathway connecting the locus coeruleus to the transentorhinal cortex (LC‐TEC) in patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD). METHODS Diffusion‐weighted MRI scans were collected for 21 AD, 20 behavioral variants of FTD (bvFTD), and 20 controls. Fractional anisotropy (FA), mean, axial, and radial diffusivities (MD, AxD, RD) were computed in the LC‐TEC pathway using a normative atlas. Atrophy was assessed using cortical thickness and correlated with microstructural measures. RESULTS We found (i) higher RD in AD than controls; (ii) higher MD, RD, and AxD, and lower FA in bvFTD than controls and AD; and (iii) a negative association between LC‐TEC MD, RD, and AxD, and entorhinal cortex (EC) thickness in bvFTD (all p

Published
2024
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4. A peripheral signature of Alzheimer’s disease featuring microbiota-gut-brain axis markers

Author

Moira Marizzoni, Peppino Mirabelli, Elisa Mombelli, Luigi Coppola, Cristina Festari, Nicola Lopizzo, Delia Luongo, Monica Mazzelli, Daniele Naviglio, Jean-Louis Blouin, Marc Abramowicz, Marco Salvatore, Michela Pievani, Annamaria Cattaneo, and Giovanni B. Frisoni

Subjects
Cognitive impairment, Alzheimer’s disease, Gut microbiota, Microbiota-gut-brain axis, Lipopolysaccharide, Endothelial dysfunction, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Increasing evidence links the gut microbiota (GM) to Alzheimer’s disease (AD) but the mechanisms through which gut bacteria influence the brain are still unclear. This study tests the hypothesis that GM and mediators of the microbiota-gut-brain axis (MGBA) are associated with the amyloid cascade in sporadic AD. Methods We included 34 patients with cognitive impairment due to AD (CI-AD), 37 patients with cognitive impairment not due to AD (CI-NAD), and 13 cognitively unimpaired persons (CU). We studied the following systems: (1) fecal GM, with 16S rRNA sequencing; (2) a panel of putative MGBA mediators in the blood including immune and endothelial markers as bacterial products (i.e., lipopolysaccharide, LPS), cell adhesion molecules (CAMs) indicative of endothelial dysfunction (VCAM-1, PECAM-1), vascular changes (P-, E-Selectin), and upregulated after infections (NCAM, ICAM-1), as well as pro- (IL1β, IL6, TNFα, IL18) and anti- (IL10) inflammatory cytokines; (3) the amyloid cascade with amyloid PET, plasma phosphorylated tau (pTau-181, for tau pathology), neurofilament light chain (NfL, for neurodegeneration), and global cognition measured using MMSE and ADAScog. We performed 3-group comparisons of markers in the 3 systems and calculated correlation matrices for the pooled group of CI-AD and CU as well as CI-NAD and CU. Patterns of associations based on Spearman’s rho were used to validate the study hypothesis. Results CI-AD were characterized by (1) higher abundance of Clostridia_UCG-014 and decreased abundance of Moryella and Blautia (p

Published
2023
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6. Exploring the role of immune pathways in the risk and development of depression in adolescence: Research protocol of the IDEA-FLAME study

Author

Valeria Mondelli, Annamaria Cattaneo, Naghmeh Nikkheslat, Laila Souza, Annabel Walsh, Zuzanna Zajkowska, Valentina Zonca, Moira Marizzoni, Helen L. Fisher, Brandon A. Kohrt, Christian Kieling, and Paola Di Meglio

Subjects
Depression, Adolescence, Cytokines, RNAseq, Flow cytometry, Immune cells, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Extensive research suggests a role for the innate immune system in the pathogenesis of depression, but most of the studies are conducted in adult populations, in high-income countries and mainly focus on the study of inflammatory proteins alone, which provides only a limited understanding of the immune pathways involved in the development of depression. The IDEA-FLAME study aims to identify immune phenotypes underlying increased risk of developing depression in adolescence in a middle-income country. To this end, we will perform deep-immunophenotyping of peripheral blood mononuclear cells and RNA genome-wide gene expression analyses in a longitudinal cohort of Brazilian adolescents stratified for depression risk. The project will involve the 3-year follow-up of an already recruited cohort of 150 Brazilian adolescents selected for risk/presence of depression on the basis of a composite risk score we developed using sociodemographic characteristics (50 adolescents with low-risk and 50 with high-risk of developing depression, and 50 adolescents with a current major depressive disorder). We will 1) test whether the risk group classification at baseline is associated with differences in immune cell frequency, phenotype and functional status, 2) test whether baseline immune markers (cytokines and immune cell markers) are associated with severity of depression at 3-year follow-up, and 3) identify changes in gene expression of immune pathways over the 3-year follow-up in adolescents with increased risk and presence of depression. Because of the exploratory nature of the study, the findings would need to be replicated in a separate and larger sample. Ultimately, this research will contribute to elucidating key immune therapeutic targets and inform the development of interventions to prevent onset of depression among adolescents.

Published
2021
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7. The Complex Molecular Picture of Gut and Oral Microbiota–Brain-Depression System: What We Know and What We Need to Know

Author

Catia Scassellati, Moira Marizzoni, Nadia Cattane, Nicola Lopizzo, Elisa Mombelli, Marco Andrea Riva, and Annamaria Cattaneo

Subjects
major depressive disorder, gut phageome, gut microbiome, oral microbiome, brain, biological molecular processes, Psychiatry, RC435-571
Abstract

Major depressive disorder (MDD) is a complex mental disorder where the neurochemical, neuroendocrine, immune, and metabolic systems are impaired. The microbiota-gut-brain axis is a bidirectional network where the central and enteric nervous systems are linked through the same endocrine, immune, neural, and metabolic routes dysregulated in MDD. Thus, gut-brain axis abnormalities in MDD patients may, at least in part, account for the symptomatic features associated with MDD. Recent investigations have suggested that the oral microbiome also plays a key role in this complex molecular picture of relationships. As on one hand there is a lot of what we know and on the other hand little of what we still need to know, we structured this review focusing, in the first place, on putting all pieces of this complex puzzle together, underlying the endocrine, immune, oxidative stress, neural, microbial neurotransmitters, and metabolites molecular interactions and systems lying at the base of gut microbiota (GM)–brain-depression interphase. Then, we focused on promising but still under-explored areas of research strictly linked to the GM and potentially involved in MDD development: (i) the interconnection of GM with oral microbiome that can influence the neuroinflammation-related processes and (ii) gut phageome (bacteria-infecting viruses). As conclusions and future directions, we discussed potentiality but also pitfalls, roadblocks, and the gaps to be bridged in this exciting field of research. By the development of a broader knowledge of the biology associated with MDD, with the inclusion of the gut/oral microbiome, we can accelerate the growth toward a better global health based on precision medicine.

Published
2021
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8. Abnormalities of Cortical Sources of Resting State Delta Electroencephalographic Rhythms Are Related to Epileptiform Activity in Patients With Amnesic Mild Cognitive Impairment Not Due to Alzheimer's Disease

Author

Claudio Babiloni, Giuseppe Noce, Carlo Di Bonaventura, Roberta Lizio, Maria Teresa Pascarelli, Federico Tucci, Andrea Soricelli, Raffaele Ferri, Flavio Nobili, Francesco Famà, Eleonora Palma, Pierangelo Cifelli, Moira Marizzoni, Fabrizio Stocchi, Giovanni B. Frisoni, and Claudio Del Percio

Subjects
amnesic mild cognitive impairment (aMCI), dementia, alzheheimer's disease, exact low-resolution brain electromagnetic source tomography (eLORETA), resting state electroencephalographic (rsEEG) rhythms, epileptiform electroencephalographic activity (EEA), Neurology. Diseases of the nervous system, RC346-429
Abstract

In the present exploratory and retrospective study, we hypothesized that cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms might be more abnormal in patients with epileptiform EEG activity (spike-sharp wave discharges, giant spikes) and amnesic mild cognitive impairment not due to Alzheimer's disease (noADMCI-EEA) than matched noADMCI patients without EEA (noADMCI-noEEA). Clinical, neuroimaging, neuropsychological, and rsEEG data in 32 noADMCI and 30 normal elderly (Nold) subjects were available in a national archive. Age, gender, and education were carefully matched among them. No subject had received a clinical diagnosis of epilepsy. Individual alpha frequency peak (IAF) was used to determine the delta, theta, and alpha frequency bands of rsEEG rhythms. Fixed beta and gamma bands were also considered. Regional rsEEG cortical sources were estimated by eLORETA freeware. Area under receiver operating characteristic (AUROC) curves indexed the accuracy of eLORETA solutions in the classification between noADMCI-EEA and noADMCI-noEEA individuals. As novel findings, EEA was observed in 41% of noADMCI patients. Furthermore, these noADMCI-EEA patients showed higher temporal delta source activities as compared to noADMCI-no EEA patients and Nold subjects. Those activities discriminated individuals of the two NoADMCI groups with an accuracy of about 70%. The significant percentage of noADMCI-EEA patients showing EEA and marked abnormalities in temporal rsEEG rhythms at delta frequencies suggest a substantial role of underlying neural hypersynchronization mechanisms in their brain dysfunctions.

Published
2020
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9. Amygdalar nuclei and hippocampal subfields on MRI: Test-retest reliability of automated volumetry across different MRI sites and vendors

Author

Giulia Quattrini, Michela Pievani, Jorge Jovicich, Marco Aiello, Núria Bargalló, Frederik Barkhof, David Bartres-Faz, Alberto Beltramello, Francesca B. Pizzini, Olivier Blin, Regis Bordet, Massimo Caulo, Manos Constantinides, Mira Didic, Antonios Drevelegas, Antonio Ferretti, Ute Fiedler, Piero Floridi, Hélène Gros-Dagnac, Tilman Hensch, Karl-Titus Hoffmann, Joost P. Kuijer, Renaud Lopes, Camillo Marra, Bernhard W. Müller, Flavio Nobili, Lucilla Parnetti, Pierre Payoux, Agnese Picco, Jean-Philippe Ranjeva, Luca Roccatagliata, Paolo M. Rossini, Marco Salvatore, Peter Schonknecht, Björn H. Schott, Julien Sein, Andrea Soricelli, Roberto Tarducci, Magda Tsolaki, Pieter J. Visser, Jens Wiltfang, Jill C. Richardson, Giovanni B. Frisoni, and Moira Marizzoni

Subjects
Amygdalar nuclei, Hippocampal subfields, Multicenter MRI study, FreeSurfer, Reliability analysis, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Background: The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults. Methods: Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1–90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (ε) and spatial overlapping coefficient (DICE) between test and retest session. Results: Significant MRI site and vendor effects (p ​0.43, p ​ ​0.80). Conclusion: Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials.

Published
2020
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10. Comparison of Bioinformatics Pipelines and Operating Systems for the Analyses of 16S rRNA Gene Amplicon Sequences in Human Fecal Samples

Author

Moira Marizzoni, Thomas Gurry, Stefania Provasi, Gilbert Greub, Nicola Lopizzo, Federica Ribaldi, Cristina Festari, Monica Mazzelli, Elisa Mombelli, Marco Salvatore, Peppino Mirabelli, Monica Franzese, Andrea Soricelli, Giovanni B. Frisoni, and Annamaria Cattaneo

Subjects
16S rRNA amplicon sequencing, QIIME2, bioconductor, UPARSE, mothur, microbiome, Microbiology, QR1-502
Abstract

Amplicon high-throughput sequencing of 16S ribosomal RNA (rRNA) gene is currently the most widely used technique to investigate complex gut microbial communities. Microbial identification might be influenced by several factors, including the choice of bioinformatic pipelines, making comparisons across studies difficult. Here, we compared four commonly used pipelines (QIIME2, Bioconductor, UPARSE and mothur) run on two operating systems (OS) (Linux and Mac), to evaluate the impact of bioinformatic pipeline and OS on the taxonomic classification of 40 human stool samples. We applied the SILVA 132 reference database for all the pipelines. We compared phyla and genera identification and relative abundances across the four pipelines using the Friedman rank sum test. QIIME2 and Bioconductor provided identical outputs on Linux and Mac OS, while UPARSE and mothur reported only minimal differences between OS. Taxa assignments were consistent at both phylum and genus level across all the pipelines. However, a difference in terms of relative abundance was identified for all phyla (p < 0.013) and for the majority of the most abundant genera (p < 0.028), such as Bacteroides (QIIME2: 24.5%, Bioconductor: 24.6%, UPARSE-linux: 23.6%, UPARSE-mac: 20.6%, mothur-linux: 22.2%, mothur-mac: 21.6%, p < 0.001). The use of different bioinformatic pipelines affects the estimation of the relative abundance of gut microbial community, indicating that studies using different pipelines cannot be directly compared. A harmonization procedure is needed to move the field forward.

Published
2020
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11. A Conformation Variant of p53 Combined with Machine Learning Identifies Alzheimer Disease in Preclinical and Prodromal Stages

Author

Giulia Abate, Marika Vezzoli, Letizia Polito, Antonio Guaita, Diego Albani, Moira Marizzoni, Emirena Garrafa, Alessandra Marengoni, Gianluigi Forloni, Giovanni B. Frisoni, Jeffrey L. Cummings, Maurizio Memo, and Daniela Uberti

Subjects
blood-based biomarker, Alzheimer’s disease, machine learning, β-amyloid, conformation variant of p53, Medicine
Abstract

Early diagnosis of Alzheimer’s disease (AD) is a crucial starting point in disease management. Blood-based biomarkers could represent a considerable advantage in providing AD-risk information in primary care settings. Here, we report new data for a relatively unknown blood-based biomarker that holds promise for AD diagnosis. We evaluate a p53-misfolding conformation recognized by the antibody 2D3A8, also named Unfolded p53 (U-p532D3A8+), in 375 plasma samples derived from InveCe.Ab and PharmaCog/E-ADNI longitudinal studies. A machine learning approach is used to combine U-p532D3A8+ plasma levels with Mini-Mental State Examination (MMSE) and apolipoprotein E epsilon-4 (APOEε4) and is able to predict AD likelihood risk in InveCe.Ab with an overall 86.67% agreement with clinical diagnosis. These algorithms also accurately classify (AUC = 0.92) Aβ+—amnestic Mild Cognitive Impairment (aMCI) patients who will develop AD in PharmaCog/E-ADNI, where subjects were stratified according to Cerebrospinal fluid (CSF) AD markers (Aβ42 and p-Tau). Results support U-p532D3A8+ plasma level as a promising additional candidate blood-based biomarker for AD.

Published
2020
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12. Plasma biomarkers for Alzheimer’s disease: a field-test in a memory clinic

Author

Daniele Altomare, Sara Stampacchia, Federica Ribaldi, Szymon Tomczyk, Claire Chevalier, Géraldine Poulain, Saina Asadi, Bianca Bancila, Moira Marizzoni, Marta Martins, Aurelien Lathuiliere, Max Scheffler, Nicholas J Ashton, Henrik Zetterberg, Kaj Blennow, Ilse Kern, Miguel Frias, Valentina Garibotto, and Giovanni B Frisoni

Subjects
Psychiatry and Mental health, Surgery, Neurology (clinical)
Abstract

BackgroundThe key Alzheimer’s disease (AD) biomarkers are traditionally measured with techniques/exams that are either expensive (amyloid-positron emission tomography (PET) and tau-PET), invasive (cerebrospinal fluid Aβ42and p-tau181), or poorly specific (atrophy on MRI and hypometabolism on fluorodeoxyglucose-PET). Recently developed plasma biomarkers could significantly enhance the efficiency of the diagnostic pathway in memory clinics and improve patient care. This study aimed to: (1) confirm the correlations between plasma and traditional AD biomarkers, (2) assess the diagnostic accuracy of plasma biomarkers as compared with traditional biomarkers, and (3) estimate the proportion of traditional exams potentially saved thanks to the use of plasma biomarkers.MethodsParticipants were 200 patients with plasma biomarkers and at least one traditional biomarker collected within 12 months.ResultsOverall, plasma biomarkers significantly correlated with biomarkers assessed through traditional techniques: up tor=0.50 (pr=0.43 (p=0.002) among tau, andr=−0.23 (p=0.001) among neurodegeneration biomarkers. Moreover, plasma biomarkers showed high accuracy in discriminating the biomarker status (normal or abnormal) determined by using traditional biomarkers: up to area under the curve (AUC)=0.87 for amyloid, AUC=0.82 for tau, and AUC=0.63 for neurodegeneration status. The use of plasma as a gateway to traditional biomarkers using cohort-specific thresholds (with 95% sensitivity and 95% specificity) could save up to 49% of amyloid, 38% of tau, and 16% of neurodegeneration biomarkers.ConclusionThe implementation of plasma biomarkers could save a remarkable proportion of more expensive traditional exams, making the diagnostic workup more cost-effective and improving patient care.

Published
2023

13. What a Single Electroencephalographic (EEG) Channel Can Tell us About Alzheimer's Disease Patients With Mild Cognitive Impairment

Author

Claudio Del Percio, Susanna Lopez, Giuseppe Noce, Roberta Lizio, Federico Tucci, Andrea Soricelli, Raffaele Ferri, Flavio Nobili, Dario Arnaldi, Francesco Famà, Carla Buttinelli, Franco Giubilei, Moira Marizzoni, Bahar Güntekin, Görsev Yener, Fabrizio Stocchi, Laura Vacca, Giovanni B. Frisoni, and Claudio Babiloni

Subjects
Cerebral Cortex, Rest, Electroencephalography, Mild Cognitive Impairment Due to Alzheimer's Disease (ADMCI), General Medicine, Classification, Bipolar rsEEG Spectral Power Density, Resting State Electroencephalographic (rsEEG) Rhythms, Neurology, Alzheimer Disease, bipolar rsEEG spectral power density, classification, mild cognitive impairment due to Alzheimer's disease (ADMCI), resting state electroencephalographic (rsEEG) rhythms, telehealth applications, Humans, Cognitive Dysfunction, Neurology (clinical), Telehealth Applications, Aged
Abstract

Abnormalities in cortical sources of resting-state eyes closed electroencephalographic (rsEEG) rhythms recorded by hospital settings (10-20 montage) with 19 scalp electrodes characterized Alzheimer's disease (AD) from preclinical to dementia stages. An intriguing rsEEG application is the monitoring and evaluation of AD progression in large populations with few electrodes in low-cost devices. Here we evaluated whether the above-mentioned abnormalities can be observed from fewer scalp electrodes in patients with mild cognitive impairment due to AD (ADMCI). Clinical and rsEEG data acquired in hospital settings (10-20 montage) from 75 ADMCI participants and 70 age-, education-, and sex-matched normal elderly controls (Nold) were available in an Italian-Turkish archive (PDWAVES Consortium; www.pdwaves.eu ). Standard spectral fast fourier transform (FFT) analysis of rsEEG data for individual delta, theta, and alpha frequency bands was computed from 6 monopolar scalp electrodes to derive bipolar C3-P3, C4-P4, P3-O1, and P4-O2 markers. The ADMCI group showed increased delta and decreased alpha power density at the C3-P3, C4-P4, P3-O1, and P4-O2 bipolar channels compared to the Nold group. Increased theta power density for ADMCI patients was observed only at the C3-P3 bipolar channel. Best classification accuracy between the ADMCI and Nold individuals reached 81% (area under the receiver operating characteristic curve) using Alpha2/Theta power density computed at the C3-P3 bipolar channel. Standard rsEEG power density computed from six posterior bipolar channels characterized ADMCI status. These results may pave the way toward diffuse clinical applications in health monitoring of dementia using low-cost EEG systems with a strict number of electrodes in lower- and middle-income countries.

Published
2022

14. Longitudinal reproducibility of default-mode network connectivity in healthy elderly participants: A multicentric resting-state fMRI study.

Author

Jorge Jovicich, Ludovico Minati, Moira Marizzoni, Rocco Marchitelli, Roser Sala-Llonch, David Bartrés-Faz, Jennifer Arnold, Jens Benninghoff, Ute Fiedler, Luca Roccatagliata, Agnese Picco, Flavio Nobili, Olivier Blin, Stephanie Bombois, Renaud Lopes, Régis Bordet, Julien Sein, Jean-Philippe Ranjeva, Mira Didic, Hélène Gros-Dagnac, Pierre Payoux, Giada Zoccatelli, Franco Alessandrini, Alberto Beltramello, Núria Bargalló, Antonio Ferretti, Massimo Caulo, Marco Aiello 0003, Carlo Cavaliere, Andrea Soricelli, Lucilla Parnetti, Roberto Tarducci, Piero Floridi, Magda Tsolaki, Manos Constantinidis, Antonios Drevelegas, Paolo Maria Rossini, Camillo Marra, Peter Schönknecht, Tilman Hensch, Karl-Titus Hoffmann, Joost P. A. Kuijer, Pieter Jelle Visser, Frederik Barkhof, and Giovanni B. Frisoni

Published
2016
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16. Faecal microbiota transplantation from Alzheimer’s participants induces impairments in hippocampal neurogenesis and cognitive behaviours in rats

Author

Stefanie Grabrucker, Moira Marizzoni, Edina Silajdžić, Nicolo Lopizzo, Elisa Mombelli, Sarah Nicolas, Sebastian Dohm-Hansen, Catia Scassellati, Davide Moretti, Melissa Rosa, Karina Hoffmann, Jane Englsih, Aonghus Lavelle, Cora O'Neill, Sandrine Thuret, Annamaria Cattaneo, and Yvonne Nolan

Abstract

The gut microbiome is emerging as an important susceptibility factor in Alzheimer’s disease (AD) possibly due to the increased prevalence of pro-inflammatory genera in gut microbiota of AD participants. Microbiota-mediated changes in cognition and adult hippocampal neurogenesis (AHN), an important process for memory which is altered in AD, position the microbiota-gut-brain axis as a key regulator of AD. However, it is unknown whether gut microbiota alterations are the cause or consequence of AD symptoms. We transplanted faecal microbiota from AD participants and age-matched controls into microbiota-depleted naïve adult rats and found impairments in AHN and associated memory tasks, which correlated with clinical cognitive scores. Discrete changes in the rat caecal and hippocampal metabolome were evident. Serum from AD participants also decreased neurogenesis in vitro and correlated with cognitive scores and pro-inflammatory genera. Our results reveal that the cognitive symptoms in AD may be due to alterations in gut microbiota, and that impaired neurogenesis may be a mechanistic link between altered gut microbiota and cognitive impairment in AD.

Published
2022

17. Faecal microbiota transplantation from Alzheimer’s participants induces impairments in neurogenesis and cognitive behaviours in rats

Author

Stefanie Grabrucker, Moira Marizzoni, Edina Silajdžić, Nicola Lopizzo, Elisa Mombelli, Sarah Nicolas, Sebastian Dohm-Hansen, Catia Scassellati, Davide Vito Moretti, Melissa Rosa, Karina Hoffmann, Jane A English, Aonghus Lavelle, Cora O’Neill, Sandrine Thuret, Annamaria Cattaneo, and Yvonne M Nolan

Abstract

The gut microbiome is emerging as an important susceptibility factor in Alzheimer’s disease (AD) possibly due to the increased prevalence of pro-inflammatory genera in gut microbiota of AD participants. Microbiota-mediated changes in cognition and adult hippocampal neurogenesis (AHN), an important process for memory which is altered in AD, position the microbiota-gut-brain axis as a key regulator of AD. However, it is unknown whether gut microbiota alterations are the cause or consequence of AD symptoms. We transplanted faecal microbiota from AD participants and age-matched controls into microbiota-depleted naïve adult rats and found impairments in AHN and associated memory tasks, which correlated with clinical cognitive scores. Discrete changes in the rat caecal and hippocampal metabolome were evident. Serum from AD participants also decreased neurogenesis in vitro and correlated with cognitive scores and pro-inflammatory genera. Our results reveal that the cognitive symptoms in AD may be due to alterations in gut microbiota, and that impaired neurogenesis may be a mechanistic link between altered gut microbiota and cognitive impairment in AD.

Published
2022

18. Short-Chain Fatty Acids and Lipopolysaccharide as Mediators Between Gut Dysbiosis and Amyloid Pathology in Alzheimer’s Disease

Author

Moira Marizzoni, Annamaria Cattaneo, Peppino Mirabelli, Cristina Festari, Nicola Lopizzo, Valentina Nicolosi, Elisa Mombelli, Monica Mazzelli, Delia Luongo, Daniele Naviglio, Luigi Coppola, Marco Salvatore, and Giovanni B. Frisoni

Abstract

Background: Metagenomic data support an association between certain bacterial strains and Alzheimer’s disease (AD), but their functional dynamics remain elusive. Objective: To investigate the association between amyloid pathology, bacterial products such as lipopolysaccharide (LPS) and short chain fatty acids (SCFAs: acetate, valerate, butyrate), inflammatory mediators, and markers of endothelial dysfunction in AD. Methods: Eighty-nine older persons with cognitive performance from normal to dementia underwent florbetapir amyloid PET and blood collection. Brain amyloidosis was measured with standardized uptake value ratio versus cerebellum. Blood levels of LPS were measured by ELISA, SCFAs by mass spectrometry, cytokines by using real-time PCR, and biomarkers of endothelial dysfunction by flow cytometry. We investigated the association between the variables listed above with Spearman’s rank test. Results: Amyloid SUVR uptake was positively associated with blood LPS (rho ≥ 0.32, p ≤ 0.006), acetate and valerate (rho ≥ 0.45, p < 0.001), pro-inflammatory cytokines (rho ≥ 0.25, p ≤ 0.012), and biomarkers of endothelial dysfunction (rho ≥ 0.25, p ≤ 0.042). In contrast, it was negatively correlated with butyrate (rho ≤ –0.42, p ≤ 0.020) and the anti-inflammatory cytokine IL10 (rho ≤ −0.26, p ≤ 0.009). Endothelial dysfunction was positively associated with pro-inflammatory cytokines, acetate and valerate(rho ≥ 0.25, p ≤ 0.045)and negatively with butyrate and IL10 levels (rho ≤ −0.25, p ≤ 0.038). Conclusion: We report a novel association between gut microbiota-related products and systemic inflammation with brain amyloidosis via endothelial dysfunction, suggesting that SCFAs and LPS represent candidate pathophysiologic links between the gut microbiota and AD pathology.

Published
2022

19. Multisite longitudinal reliability of tract-based spatial statistics in diffusion tensor imaging of healthy elderly subjects.

Author

Jorge Jovicich, Moira Marizzoni, Beatriz Bosch, David Bartrés-Faz, Jennifer Arnold, Jens Benninghoff, Jens Wiltfang, Luca Roccatagliata, Agnese Picco, Flavio Nobili, Olivier Blin, Stephanie Bombois, Renaud Lopes, Régis Bordet, Valérie Chanoine, Jean-Philippe Ranjeva, Mira Didic, Hélène Gros-Dagnac, Pierre Payoux, Giada Zoccatelli, Franco Alessandrini, Alberto Beltramello, Núria Bargalló, Antonio Ferretti, Massimo Caulo, Marco Aiello 0003, Monica Ragucci, Andrea Soricelli, Nicola Salvadori, Roberto Tarducci, Piero Floridi, Magda Tsolaki, Manos Constantinidis, Antonios Drevelegas, Paolo Maria Rossini, Camillo Marra, Josephin Otto, Martin Reiss-Zimmermann, Karl-Titus Hoffmann, Samantha Galluzzi, and Giovanni B. Frisoni

Published
2014
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20. Alzheimer's Disease with Epileptiform EEG Activity: Abnormal Cortical Sources of Resting State Delta Rhythms in Patients with Amnesic Mild Cognitive Impairment

Author

Claudio Babiloni, Giuseppe Noce, Carlo Di Bonaventura, Roberta Lizio, Ali Eldellaa, Federico Tucci, Enrico M. Salamone, Raffaele Ferri, Andrea Soricelli, Flavio Nobili, Francesco Famà, Dario Arnaldi, Eleonora Palma, Pierangelo Cifelli, Moira Marizzoni, Fabrizio Stocchi, Giuseppe Bruno, Giancarlo Di Gennaro, Giovanni B. Frisoni, and Claudio Del Percio

Subjects
Cerebral Cortex, Epileptiform EEG activity, exact low-resolution brain electromagnetic source tomography, mild cognitive impairment due to Alzheimer’s disease, resting state electroencephalographic rhythms, General Neuroscience, Rest, Electroencephalography, General Medicine, Psychiatry and Mental health, Clinical Psychology, Delta Rhythm, Alzheimer Disease, Humans, Cognitive Dysfunction, Geriatrics and Gerontology, Aged
Abstract

Background: Patients with amnesic mild cognitive impairment due to Alzheimer’s disease (ADMCI) typically show a “slowing” of cortical resting-state eyes-closed electroencephalographic (rsEEG) rhythms. Some of them also show subclinical, non-convulsive, and epileptiform EEG activity (EEA) with an unclear relationship with that “slowing.” Objective: Here we tested the hypothesis that the “slowing” of rsEEG rhythms is related to EEA in ADMCI patients. Methods: Clinical and instrumental datasets in 62 ADMCI patients and 38 normal elderly (Nold) subjects were available in a national archive. No participant had received a clinical diagnosis of epilepsy. The eLORETA freeware estimated rsEEG cortical sources. The area under the receiver operating characteristic curve (AUROCC) indexed the accuracy of eLORETA solutions in the classification between ADMCI-EEA and ADMCI-noEEA individuals. Results: EEA was observed in 15% (N = 8) of the ADMCI patients. The ADMCI-EEA group showed: 1) more abnormal Aβ42 levels in the cerebrospinal fluid as compared to the ADMCI-noEEA group and 2) higher temporal and occipital delta (

Published
2022

21. Brain morphometry reproducibility in multi-center 3 T MRI studies: A comparison of cross-sectional and longitudinal segmentations.

Author

Jorge Jovicich, Moira Marizzoni, Roser Sala-Llonch, Beatriz Bosch, David Bartrés-Faz, Jennifer Arnold, Jens Benninghoff, Jens Wiltfang, Luca Roccatagliata, Flavio Nobili, Tilman Hensch, Anja Tränkner, Peter Schönknecht, Melanie Leroy, Renaud Lopes, Régis Bordet, Valérie Chanoine, Jean-Philippe Ranjeva, Mira Didic, Hélène Gros-Dagnac, Pierre Payoux, Giada Zoccatelli, Franco Alessandrini, Alberto Beltramello, Núria Bargalló, Olivier Blin, and Giovanni B. Frisoni

Published
2013
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22. Reactivity of posterior cortical electroencephalographic alpha rhythms during eyes opening in cognitively intact older adults and patients with dementia due to Alzheimer's and Lewy body diseases

Author

Claudio Babiloni, Ivan Lorenzo, Roberta Lizio, Susanna Lopez, Federico Tucci, Raffaele Ferri, Andrea Soricelli, Flavio Nobili, Dario Arnaldi, Francesco Famà, Carla Buttinelli, Franco Giubilei, Virginia Cipollini, Marco Onofrj, Fabrizio Stocchi, Laura Vacca, Peter Fuhr, Ute Gschwandtner, Gerhard Ransmayr, Dag Aarsland, Lucilla Parnetti, Moira Marizzoni, Fabrizia D'Antonio, Carlo De Lena, Bahar Güntekin, Ebru Yıldırım, Lutfu Hanoğlu, Görsev Yener, Duygu Hünerli Gündüz, John Paul Taylor, Julia Schumacher, Ian McKeith, Giovanni B. Frisoni, Maria Francesca De Pandis, Laura Bonanni, Claudio Del Percio, and Giuseppe Noce

Subjects
Lewy Body Disease, lzheimer's disease (AD), Aging, Rest, Dementia with Lewy Bodies (DLB), dementia with Lewy Bodies (DLB), desynchronization of alpha rhythms, exact low-resolution brain electromagnetic source tomography (eLORETA), eyes closed, eyes open, resting state electroencephalographic (EEG) rhythms, Alzheimer Disease, mental disorders, Humans, Cognitive Dysfunction, Aged, Cerebral Cortex, Eyes open, General Neuroscience, Resting State Electroencephalographic (EEG) Rhythms, Electroencephalography, Exact Low-Resolution Brain Electromagnetic Source Tomography (eLORETA), Alpha Rhythm, Eyes closed, Alzheimer's disease (AD), Desynchronization of Alpha Rhythms, Lewy Bodies, Neurology (clinical), Geriatrics and Gerontology, Developmental Biology
Abstract

Please modify the Abstract as follows:Here we tested if the reactivity of posterior resting-state electroencephalographic (rsEEG) alpha rhythms from the eye-closed to the eyes-open condition may differ in patients with dementia due to Lewy Bodies (DLB) and Alzheimer's disease (ADD) as a functional probe of the dominant neural synchronization mechanisms regulating the vigilance in posterior visual systems.We used clinical, demographical, and rsEEG datasets in 28 older adults (Healthy), 42 DLB, and 48 ADD participants. The eLORETA freeware was used to estimate cortical rsEEG sources.Results showed a substantial (> -10%) reduction in the posterior alpha activities during the eyes-open condition in 24 Healthy, 26 ADD, and 22 DLB subjects. There were lower reductions in the posterior alpha activities in the ADD and DLB groups than in the Healthy group. That reduction in the occipital region was lower in the DLB than in the ADD group.These results suggest that DLB patients may suffer from a greater alteration in the neural synchronization mechanisms regulating vigilance in occipital cortical systems compared to ADD patients. H2020 Marie S. Curie ITN-ETN project Italian Ministry of Health to the IRCCS SDN of Naples, IRCCS OASI of Troina, and IRCCS San Raffaele Pisana of Rome

Published
2022

23. Resting State Electroencephalographic Alpha Rhythms Predict and are Sensitive to Alzheimer’S Disease Mild Cognitive Impairment Progression at a 6-Month Follow-Up

Author

Claudio Babiloni, Dharmendra Jakhar, Federico Tucci, Claudio Del Percio, Susanna Lopez, Andrea Soricelli, Marco Salvatore, Raffaele Ferri, Valentina Catania, Federico Massa, Dario Arnaldi, Francesco Famà, Bahar Güntekin, Görsev Yener, Fabrizio Stocchi, Laura Vacca, Moira Marizzoni, Franco Giubilei, Ebru Yıldırım, Luftu Hanoglu, Duygu Hünerli-Gündüz, Giovanni Frisoni, and Giuseppe Noce

Subjects
History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Published
2022

24. Poor Reactivity of Posterior Electroencephalographic Alpha Rhythms During the Eyes Open Condition in Patients with Dementia Due to Parkinson’s Disease

Author

Claudio Babiloni, Giuseppe Noce, Federico Tucci, Raffaele Ferri, Simonetta Panerai, Valentina Catania, Andrea Soricelli, Marco Salvatore, Flavio Nobili, Dario Arnaldi, Francesco Famà, Carla Buttinelli, Franco Giubilei, Marco Onofrj, Fabrizio Stocchi, Laura Vacca, Fabiana Radicati, Peter Fuhr, Ute Gschwandtner, Gerhard Ransmayr, Lucilla Parnetti, Moira Marizzoni, Fabrizia D'Antonio, Giuseppe Bruno, Carlo De Lena, Bahar Güntekin, Ebru Yıldırım, Luftu Hanoglu, Görsev Yener, Duygu Hünerli Gündüz, John Paul Taylor, Julia Schumacher, Ian McKeith, Giovanni Frisoni, Angelo Antonini, Florinda Ferreri, Laura Bonanni, Maria Francesca De Pandis, and Claudio Del Percio

Subjects
History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Published
2022

25. Data‐driven cut‐off values for 18 ‐F‐AV‐45 tau PET staging in AD

Author

Giulia Quattrini, Clarissa Ferrari, Michela Pievani, Giovanni B. Frisoni, and Moira Marizzoni

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2021

26. Relationship between cortical neural synchronization at alpha resting‐state electroencephalographic rhythms and education attainment in normal elderly subjects and patients with amnestic mild cognitive impairment due to Alzheimer’s disease

Author

Giuseppe Noce, Claudio Babiloni, Raffaele Ferri, Roberta Lizio, Susanna Lopez, Ivan Lorenzo, Federico Tucci, Andrea Soricelli, Flavio Mariano Nobili, Dario Arnaldi, Francesco Famà, Franco Giubilei, Moira Marizzoni, Bahar Güntekin, Gorsev Yener, Fabrizio Stocchi, Giovanni Frisoni, and Claudio Del Percio

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2021

27. Cortical arousal is differently related with resting‐state electroencephalographic delta rhythms in healthy seniors and in patients with dementia due to Alzheimer’s disease

Author

Susanna Lopez, Claudio Babiloni, Raffaele Ferri, Giuseppe Noce, Roberta Lizio, Andrea Soricelli, Flavio Mariano Nobili, Franco Giubilei, Moira Marizzoni, Bahar Güntekin, Gorsev Yener, Giovanni B Frisoni, and Claudio Del Percio

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2021

29. Resting‐state alpha electroencephalographic rhythms are differently related to gender in cognitively unimpaired seniors and in patients with amnestic mild cognitive impairment due to Alzheimer’s disease

Author

Ivan Lorenzo, Claudio Babiloni, Giuseppe Noce, Raffaele Ferri, Roberta Lizio, Susanna Lopez, Federico Tucci, Andrea Soricelli, Flavio Mariano Nobili, Dario Arnaldi, Francesco Famà, Franco Giubilei, Moira Marizzoni, Bahar Güntekin, Gorsev Yener, Fabrizio Stocchi, Giovanni Frisoni, and Claudio Del Percio

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2021

30. Reduction in posterior cortical alpha rhythms during eye opening is more abnormal in patients with dementia due to Lewy bodies than Alzheimer’s disease: An EEG study

Author

Claudio Babiloni, Giuseppe Noce, Ivan Lorenzo, Raffaele Ferri, Roberta Lizio, Andrea Soricelli, Flavio Mariano Nobili, Carla Buttinelli, Franco Giubilei, Peter Fuhr, Ute Gschwandtner, Gerhard Ransmayr, Moira Marizzoni, Fabrizia D'Antonio, Carlo de Lena, Gorsev Yener, Derya Durusu Emek‐Savas, Fabrizio Stocchi, Giovanni B Frisoni, Maria Francesca De Pandis, Claudio Del Percio, and Susanna Lopez

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2021

31. Patients with amnesic mild cognitive impairment due to Alzheimer's disease and with epileptiform‐like signatures showed abnormal cortical sources of resting state delta EEG rhythms: An EEG study

Author

Federico Tucci, Claudio Babiloni, Giuseppe Noce, Carlo Di Bonaventura, Roberta Lizio, Ivan Lorenzo, Andrea Soricelli, Raffaele Ferri, Flavio Nobili, Francesco Famà, Dario Arnaldi, Eleonora Palma, Pierangelo Cifelli, Moira Marizzoni, Fabrizio Stocchi, Giovanni Frisoni, and Claudio Del Percio

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2021

32. Relationship between resting state alpha electroencephalographic rhythms and aging in cognitively unimpaired seniors and patients with mild cognitive impairment due to Alzheimer’s disease and amnestic mild cognitive impairment

Author

Claudio Del Percio, Roberta Lizio, Giuseppe Noce, Susanna Lopez, Andrea Soricelli, Raffaele Ferri, Bahar Güntekin, Gorsev Yener, Moira Marizzoni, Giovanni B Frisoni, and Claudio Babiloni

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2021

33. Social isolation in adolescence and long-term changes in the gut microbiota composition and in the hippocampal inflammation: Implications for psychiatric disorders - Dirk Hellhammer Award Paper 2021

Author

Stefania Provasi, Marco A. Riva, Nicola Lopizzo, Monica Mazzelli, Moira Marizzoni, Veronica Begni, Annamaria Cattaneo, and Luigimaria Borruso

Subjects
Male, Endocrinology, Diabetes and Metabolism, Awards and Prizes, Hippocampus, Physiology, Inflammation, Biology, Hippocampal formation, Gut flora, Endocrinology, Immune system, medicine, Animals, Social isolation, Biological Psychiatry, Endocrine and Autonomic Systems, Physiological condition, Mental Disorders, biology.organism_classification, Gastrointestinal Microbiome, Rats, Psychiatry and Mental health, Social deprivation, Social Isolation, Female, medicine.symptom
Abstract

Exposure to early adverse experiences induces persistent changes in physiological, emotional and behavioural functions predisposing the individual to an enhanced vulnerability to develop different disorders during lifespan. The adverse outcomes depend upon the timing of the stressful experiences, and in this contest, adolescence represents a key sensitive period for brain development. Among the biological systems involved, gut microbiota has recently been proposed to act on the interplay between the stress response, brain functions and immune system, through the gut-brain axis communication. In the current study we aimed to evaluate, in a preclinical model, changes over time in the microbiota community structure in physiological condition and in response to stress during adolescence. We also aimed to correlate the microbiota composition to the inflammatory status in brain. We used the preclinical model of social deprivation in rats during adolescence, based on the lack of all social contacts, for four weeks after weaning, followed by re-socialization until adulthood. We collected fecal samples at different post-natal days to investigate the short- and long-lasting effects of social isolation on gut microbiota composition and we collected brain areas (dorsal and ventral hippocampus) samples at killing to measure a panel of inflammatory and microglia activation markers. 16 S metataxonomic sequencing analysis revealed that microbial changes were influenced by age in both isolated and controls rats, regardless of sex, whereas social isolation impacted the microbial composition in a sex-dependent manner. A multivariate analysis showed that social isolation induced short-term gut microbiota alterations in females but not in males. We also identified several stress-related genera associated with social isolation condition. In brain areas we found a specific inflammatory pattern, in dorsal and ventral hippocampus, that significantly correlated with gut microbiota composition. Overall, in this study we reported a novel sex-specific association between gut microbiota composition and inflammatory response related to social isolation paradigm during adolescence, suggesting that stressful experiences during this sensitive period could have a long-lasting impact on the development of different biological systems that could in turn influence the vulnerability to develop mental disorders later in life.

Published
2021

34. Convergent and Discriminant Validity of Default Mode Network and Limbic Network Perfusion in Amnestic Mild Cognitive Impairment Patients

Author

Marco Salvatore, Marco Aiello, Diego Albani, Ilaria Boscolo Galazzo, Olivier Blin, Pradeep J. Nathan, Francesca B. Pizzini, Melissa Romano, Andrea Soricelli, Mira Didic, Gianluigi Forloni, Jill C. Richardson, Michela Pievani, Giovanni B. Frisoni, Jorge Jovicich, Giulia Quattrini, Moira Marizzoni, Xavier Golay, Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia = University of Brescia (UniBs), University of Brescia, Università degli studi di Verona = University of Verona (UNIVR), IRCCS SDN Napoli, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Università degli Studi di Napoli 'Parthenope' = University of Naples (PARTHENOPE), IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri' [Milan, Italy], Assistance Publique - Hôpitaux de Marseille (APHM), UCL Institute of Neurology, Queen Square [London], University of Trento [Trento], University of Cambridge [UK] (CAM), GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), and Université de Genève = University of Geneva (UNIGE)

Subjects
0301 basic medicine, Apolipoprotein E, Male, medicine.medical_specialty, Perfusion scanning, Hippocampus, Alzheimer’s disease, arterial spin labeling, brain perfusion, default mode network, limbic network, mild cognitive impairment, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Internal medicine, medicine, Limbic System, Memory impairment, Humans, Cognitive Dysfunction, Default mode network, Alzheimer's disease, Aged, Amnesia, Biomarkers, Cerebrovascular Circulation, Female, Magnetic Resonance Imaging, Default Mode Network, Perfusion, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, General Neuroscience, Discriminant validity, General Medicine, Hyperintensity, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Convergent validity, Cerebral blood flow, Cardiology, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Abstract

International audience; Background: Previous studies reported default mode network (DMN) and limbic network (LIN) brain perfusion deficits in patients with amnestic mild cognitive impairment (aMCI), frequently a prodromal stage of Alzheimer’s disease (AD). However, the validity of these measures as AD markers has not yet been tested using MRI arterial spin labeling (ASL). Objective: To investigate the convergent and discriminant validity of DMN and LIN perfusion in aMCI. Methods: We collected core AD markers (amyloid-β 42 [Aβ42], phosphorylated tau 181 levels in cerebrospinal fluid [CSF]), neurodegenerative (hippocampal volumes and CSF total tau), vascular (white matter hyperintensities), genetic (apolipoprotein E [APOE] status), and cognitive features (memory functioning on Paired Associate Learning test [PAL]) in 14 aMCI patients. Cerebral blood flow (CBF) was extracted from DMN and LIN using ASL and correlated with AD features to assess convergent validity. Discriminant validity was assessed carrying out the same analysis with AD-unrelated features, i.e., somatomotor and visual networks’ perfusion, cerebellar volume, and processing speed. Results: Perfusion was reduced in the DMN (F = 5.486, p = 0.039) and LIN (F = 12.678, p = 0.004) in APOE ɛ4 carriers compared to non-carriers. LIN perfusion correlated with CSF Aβ42 levels (r = 0.678, p = 0.022) and memory impairment (PAL, number of errors, r = –0.779, p = 0.002). No significant correlation was detected with tau, neurodegeneration, and vascular features, nor with AD-unrelated features. Conclusion: Our results support the validity of DMN and LIN ASL perfusion as AD markers in aMCI, indicating a significant correlation between CBF and amyloidosis, APOE ɛ4, and memory impairment.

Published
2021

35. Exploring the role of immune pathways in the risk and development of depression in adolescence : research protocol of the IDEA-FLAME study

Author

Christian Kieling, Moira Marizzoni, Zuzanna Zajkowska, Valeria Mondelli, Brandon A. Kohrt, Helen L. Fisher, Laila Souza, Naghmeh Nikkheslat, Annamaria Cattaneo, Annabel Walsh, Valentina Zonca, and Paola Di Meglio

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, Study Protocol, Immune system, adolescence, cytokines, depression, flow cytometry, immune cells, RNAseq, RNA seq, Medicine, RNA-Seq, Flow cytometry, Protocol (object-oriented programming), Depression (differential diagnoses), Adolescente, General Environmental Science, business.industry, Depression, Immune cells, Citocinas, Adolescence, Biomarcadores, Settore BIO/14 - Farmacologia, General Earth and Planetary Sciences, Cytokines, business, Citometria de fluxo, Clinical psychology, RC321-571
Abstract

Extensive research suggests a role for the innate immune system in the pathogenesis of depression, but most of the studies are conducted in adult populations, in high-income countries and mainly focus on the study of inflammatory proteins alone, which provides only a limited understanding of the immune pathways involved in the development of depression. The IDEA-FLAME study aims to identify immune phenotypes underlying increased risk of developing depression in adolescence in a middle-income country. To this end, we will perform deep-immunophenotyping of peripheral blood mononuclear cells and RNA genome-wide gene expression analyses in a longitudinal cohort of Brazilian adolescents stratified for depression risk. The project will involve the 3-year follow-up of an already recruited cohort of 150 Brazilian adolescents selected for risk/presence of depression on the basis of a composite risk score we developed using sociodemographic characteristics (50 adolescents with low-risk and 50 with high-risk of developing depression, and 50 adolescents with a current major depressive disorder). We will 1) test whether the risk group classification at baseline is associated with differences in immune cell frequency, phenotype and functional status, 2) test whether baseline immune markers (cytokines and immune cell markers) are associated with severity of depression at 3-year follow-up, and 3) identify changes in gene expression of immune pathways over the 3-year follow-up in adolescents with increased risk and presence of depression. Because of the exploratory nature of the study, the findings would need to be replicated in a separate and larger sample. Ultimately, this research will contribute to elucidating key immune therapeutic targets and inform the development of interventions to prevent onset of depression among adolescents., Highlights • IDEA-FLAME study aims to identify immune phenotypes of depression risk in adolescence. • IDEA-RiSCo is a cohort of adolescents stratified for risk of developing depression. • The study will help to identify immune therapeutic targets for adolescent depression.

Published
2021

36. Resting State Alpha Electroencephalographic Rhythms Are Affected by Sex in Cognitively Unimpaired Seniors and Patients with Alzheimer's Disease and Amnesic Mild Cognitive Impairment: A Retrospective and Exploratory Study

Author

Giuseppe Noce, Claudio Babiloni, Roberta Lizio, Moira Marizzoni, Raffaele Ferri, Susanna Lopez, Lutfu Hanoglu, Fabrizio Stocchi, Laura Vacca, Fernando Díaz, Paolo Onorati, Andrea Soricelli, Bahar Güntekin, Dario Arnaldi, Ebru Yıldırım, Claudio Del Percio, Francesco Famà, Flavio Nobili, Fernando Maestú, Montserrat Zurrón, Virginia Cipollini, Carla Buttinelli, Giovanni B. Frisoni, Duygu Hünerli Gündüz, Federico Tucci, Görsev Yener, Franco Giubilei, and Ivan Lorenzo

Subjects
Male, medicine.medical_specialty, Cognitive Neuroscience, media_common.quotation_subject, Rest, Exploratory research, Alpha (ethology), Disease, Audiology, Affect (psychology), Cellular and Molecular Neuroscience, Cerebrospinal fluid, Rhythm, Alzheimer Disease, medicine, Humans, sex, Cognitive Dysfunction, media_common, Aged, Retrospective Studies, Cerebral Cortex, Resting state fMRI, business.industry, resting state electroencephalographic (rsEEG) rhythms, exact low-resolution brain electromagnetic source tomography (eLORETA), mild cognitive impairment due to Alzheimer’s disease (ADMCI), Electroencephalography, Alpha Rhythm, Female, business, Vigilance (psychology)
Abstract

In the present retrospective and exploratory study, we tested the hypothesis that sex may affect cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms recorded in normal elderly (Nold) seniors and patients with Alzheimer’s disease and mild cognitive impairment (ADMCI). Datasets in 69 ADMCI and 57 Nold individuals were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands and fixed beta (14–30 Hz) and gamma (30–40 Hz) bands. Each group was stratified into matched females and males. The sex factor affected the magnitude of rsEEG source activities in the Nold seniors. Compared with the males, the females were characterized by greater alpha source activities in all cortical regions. Similarly, the parietal, temporal, and occipital alpha source activities were greater in the ADMCI-females than the males. Notably, the present sex effects did not depend on core genetic (APOE4), neuropathological (Aβ42/phospho-tau ratio in the cerebrospinal fluid), structural neurodegenerative and cerebrovascular (MRI) variables characterizing sporadic AD-related processes in ADMCI seniors. These results suggest the sex factor may significantly affect neurophysiological brain neural oscillatory synchronization mechanisms underpinning the generation of dominant rsEEG alpha rhythms to regulate cortical arousal during quiet vigilance.

Published
2021

37. Accuracy and reproducibility of automated white matter hyperintensities segmentation with lesion segmentation tool: A European multi-site 3T study

Author

Bernhard W. Müller, Daniele Altomare, Marco Salvatore, Renaud Lopes, Paolo Maria Rossini, Jens Wiltfang, Moira Marizzoni, Martina Montalti, Stéphanie Bombois, Giovanni B. Frisoni, Clarissa Ferrari, Karl Titus Hoffmann, Camillo Marra, Massimo Caulo, Francesca B. Pizzini, David Bartrés-Faz, Ute Fiedler, Antonio Ferretti, Mira Didic, Manos Constantinidis, Andrea Soricelli, Federica Ribaldi, Joost P.A. Kuijer, Carlo Cavaliere, Antonios Drevelegas, Flavio Nobili, Piero Floridi, Luca Roccatagliata, Julien Sein, Régis Bordet, Franco Alessandrini, Pierre Payoux, Roberto Tarducci, Jorge Jovicich, Olivier Blin, Agnese Picco, Jean-Philippe Ranjeva, Frederik Barkhof, Beatriz Bosch, Magda Tsolaki, Pieter Jelle Visser, Lucilla Parnetti, Tilman Hensch, Jill C. Richardson, Núria Bargalló, Anna Mega, Helene Gros-Dagnac, Marco Aiello, Peter Schönknecht, Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia [Brescia], Laboratory of Neuroimaging of aging, Memory clinic and LANVIE, Geneva University Hospital and Geneva University, Center for Mind/Brain Sciences (CIMEC), University of Trento [Trento], Dipartimento di Neuroscienze, riabilitazione, oftalmologia, genetica e scienze materno-infantili [Genova] (DINOGMI), Universita degli studi di Genova, Department of Diagnostics and Public Health [Verona] (UNIVR | DDSP), University of Verona (UNIVR), IRCCS SDN Napoli, Department of Clinic Sciences and Bioimaging, University G. d'Annunzio Chieti-Pescara, Interbalkan Medical Center of Thessaloniki, Dept. of Child and Adolescent Psychiatry and Psychology, Institut Clinic of Neurosciences IDIBAPS (Institut d'Investigacions Biomèdiques August Pi Sunyer), Hospital Clínic Universitari of Barcelona, Department of Child and Adolescent Psychiatry and Psychotherapy, LVR-Klinikum Essen, Universität Duisburg-Essen [Essen], Department of Neuroscience, Catholic University, Roma, Centre for Medical Image Computing (CMIC), University College of London [London] (UCL), Department of Radiology and Nuclear Medicine [Amsterdam], VU University Medical Center [Amsterdam], Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), University Medical Center Göttingen (UMG), Department of Neuroradiology, University Hospital Leipzig, Section of Neurology, Centre for Memory Disturbances, University of Perugia, Institut de Neurosciences des Systèmes (INS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Neurology Department, Hospital Clinic, IDIBAPS, Facultad de Medicina, Barcelona, Dept. Neuroscience & Neurorehabilitation, IRCCS-San Raffaele-Pisana, Rome, University of Leipzig Medical Center, Neuroradiology Unit, Perugia General Hospital, Perugia, Alzheimer Center Amsterdam, Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Medical Physics Unit, Perugia General Hospital, Perugia, Department of Psychiatry and Psychotherapy, University of Leipzig Medical Center, Leipzig, LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Università degli Studi di Brescia = University of Brescia (UniBs), Università degli studi di Genova = University of Genoa (UniGe), Università degli studi di Verona = University of Verona (UNIVR), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Leipzig University, Università degli Studi di Perugia = University of Perugia (UNIPG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lille Neurosciences & Cognition - U 1172 (LilNCog), Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neuroinfection & -inflammation, Neurology, and Amsterdam Neuroscience - Neurodegeneration

Subjects
Adult, Male, Aging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Image Processing, Medizin, Biomedical Engineering, Biophysics, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Automation, 0302 clinical medicine, Computer-Assisted, Sørensen–Dice coefficient, Image Processing, Computer-Assisted, White matter hyperintensities, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Segmentation, Lesion segmentation toolbox, ComputingMilieux_MISCELLANEOUS, Accuracy, Reproducibility, Lesion segmentation, business.industry, Lesion growth, Automated segmentation algorithms, Multi site, Reproducibility of Results, Gold standard (test), White Matter, Magnetic Resonance Imaging, Hyperintensity, Settore MED/26 - NEUROLOGIA, Cross-Sectional Studies, Algorithms, Female, Nuclear medicine, business, 030217 neurology & neurosurgery
Abstract

Brain vascular damage accumulate in aging and often manifest as white matter hyperintensities (WMHs) on MRI. Despite increased interest in automated methods to segment WMHs, a gold standard has not been achieved and their longitudinal reproducibility has been poorly investigated. The aim of present work is to evaluate accuracy and reproducibility of two freely available segmentation algorithms. A harmonized MRI protocol was implemented in 3T-scanners across 13 European sites, each scanning five volunteers twice (test-retest) using 2D-FLAIR. Automated segmentation was performed using Lesion segmentation tool algorithms (LST): the Lesion growth algorithm (LGA) in SPM8 and 12 and the Lesion prediction algorithm (LPA). To assess reproducibility, we applied the LST longitudinal pipeline to the LGA and LPA outputs for both the test and retest scans. We evaluated volumetric and spatial accuracy comparing LGA and LPA with manual tracing, and for reproducibility the test versus retest. Median volume difference between automated WMH and manual segmentations (mL) was −0.22[IQR = 0.50] for LGA-SPM8, −0.12[0.57] for LGA-SPM12, −0.09[0.53] for LPA, while the spatial accuracy (Dice Coefficient) was 0.29[0.31], 0.33[0.26] and 0.41[0.23], respectively. The reproducibility analysis showed a median reproducibility error of 20%[IQR = 41] for LGA-SPM8, 14% [31] for LGA-SPM12 and 10% [27] with the LPA cross-sectional pipeline. Applying the LST longitudinal pipeline, the reproducibility errors were considerably reduced (LGA: 0%[IQR = 0], p < 0.001; LPA: 0% [3], p < 0.001) compared to those derived using the cross-sectional algorithms. The DC using the longitudinal pipeline was excellent (median = 1) for LGA [IQR = 0] and LPA [0.02]. LST algorithms showed moderate accuracy and good reproducibility. Therefore, it can be used as a reliable cross-sectional and longitudinal tool in multi-site studies.

Published
2021

38. Amygdalar nuclei and hippocampal subfields on MRI: Test‐retest reliability of automated segmentation in old and young healthy volunteers

Author

Agnese Picco, Núria Bargalló, Antonios Drevelegas, Mira Didic, Régis Bordet, Moira Marizzoni, Bernhard W. Müller, Piero Floridi, Björn H. Schott, Michela Pievani, Giovanni B. Frisoni, Jill C. Richardson, Alberto Beltramello, Tilman Hensch, Marco Salvatore, Flavio Nobili, Pierre Payoux, Roberto Tarducci, Jorge Jovicich, Magda Tsolaki, Karl-Titus Hoffmann, Jens Wiltfang, Camillo Marra, Renaud Lopes, Jean-Philippe Ranjeva, Pieter Jelle Visser, Giulia Quattrini, Lucilla Parnetti, Manos Constantinides, Frederik Barkhof, David Bartrés-Faz, Francesca B. Pizzini, Julien Sein, Antonio Ferretti, Olivier Blin, Ute Fiedler, Luca Roccatagliata, Massimo Caulo, Andrea Soricelli, Paolo Maria Rossini, Joost P.A. Kuijer, Helene Gros-Dagnac, Marco Aiello, and Peter Schönknecht

Subjects
medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Automated segmentation, Hippocampal formation, Audiology, Test (assessment), Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neuroimaging, Healthy volunteers, Medicine, Neurology (clinical), Geriatrics and Gerontology, business, Brain aging, Reliability (statistics)
Published
2020

39. Different abnormalities of electroencephalographic (EEG) markers in quiet wakefulness are related to visual hallucinations in patients with Parkinson’s and Lewy body diseases

Author

Claudio Babiloni, Susanna Lopez, Maria Teresa Pascarelli, Roberta Lizio, Giuseppe Noce, Raffaele Ferri, Andrea Soricelli, Flavio Mariano Nobili, Dario Arnaldi, Francesco Famà, Francesco Orzi, Carla Buttinelli, Franco Giubilei, Marco Salvetti, Virginia Cipollini, Laura Bonanni, Raffaella Franciotti, Marco Onofrj, Peter Fuhr, Ute Gschwandtner, Gerhard Ransmayr, Dag Aarsland, Lucilla Parnetti, Lucia Farotti, Moira Marizzoni, Fabrizia D'Antonio, Carlo de Lena, Bahar Güntekin, Lutfu Hanoğlu, Görsev Yener, Derya Durusu Emek‐Savas, Antonio Ivano Triggiani, John‐Paul Taylor, Ian McKeith, Fabrizio Stocchi, Laura Vacca, Harald Hampel, Giovanni B Frisoni, Maria Francesca De Pandis, and Claudio Del Percio

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2020

40. Identification of clinical phenotypes of Alzheimer’s disease through the gut microbiota

Author

Marco Salvatore, Peppino Mirabelli, Delia Luongo, Moira Marizzoni, Elisa Mombelli, Annamaria Cattaneo, and Giovanni B. Frisoni

Subjects
biology, Epidemiology, business.industry, Health Policy, Neuropsychology, Disease, Gut flora, biology.organism_classification, medicine.disease, Bioinformatics, Phenotype, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Dementia, Identification (biology), Neurology (clinical), Geriatrics and Gerontology, Cognitive decline, business
Published
2020

41. Abnormalities of cortical neural synchronization mechanisms in subjects with mild cognitive impairment due to Alzheimer's disease and epileptiform‐like signatures

Author

Eleonora Palma, Moira Marizzoni, Claudio Babiloni, Giovanni B. Frisoni, Francesco Famà, Pierangelo Cifelli, Raffaele Ferri, Claudio Del Percio, Giuseppe Noce, Andrea Soricelli, Carlo Di Bonaventura, Roberta Lizio, and Flavio Nobili

Subjects
Epidemiology, business.industry, Health Policy, Disease, Neural synchronization, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Neurology (clinical), Geriatrics and Gerontology, Cognitive impairment, business, Neuroscience
Published
2020

42. APOE‐e4, microbiota and inflammation in healthy elderly

Author

Valentina Nicolosi, Peppino Mirabelli, Moira Marizzoni, Paulina Andryszak, Elisa Mombelli, Annamaria Cattaneo, Giovanni B. Frisoni, Pascale Roux-Lombard, and Marco Salvatore

Subjects
Epidemiology, Basic science, business.industry, Health Policy, Inflammation, Healthy elderly, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Immunology, medicine, Neurology (clinical), Geriatrics and Gerontology, medicine.symptom, business
Published
2020

43. Association between microbiota dysbiosis and endothelial dysfunction in Alzheimer’s disease: An in vivo cross‐sectional study

Author

Marco Salvatore, Peppino Mirabelli, Monica Mazzelli, Delia Luongo, Annamaria Cattaneo, Moira Marizzoni, and Giovanni B. Frisoni

Subjects
Epidemiology, Basic science, business.industry, Cross-sectional study, Health Policy, Inflammation, Disease, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, In vivo, Immunology, medicine, Neurology (clinical), Geriatrics and Gerontology, Endothelial dysfunction, medicine.symptom, business, Dysbiosis
Published
2020

44. Effect of a probiotic administration on inflammatory profile and clinical features in patients with Alzheimer’s disease

Author

Nicola Lopizzo, Elisa Mombelli, Peppino Mirabelli, Moira Marizzoni, Delia Luongo, Marco Salvatore, Annamaria Cattaneo, and Giovanni B. Frisoni

Subjects
medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Disease, Gastroenterology, law.invention, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Probiotic, Developmental Neuroscience, law, Internal medicine, medicine, In patient, Neurology (clinical), Geriatrics and Gerontology, business, Administration (government)
Published
2020

45. lncRNAs as a novel source of diagnostic applications for early Alzheimer’s disease and other dementia types

Author

Moira Marizzoni, Hüseyin Firat, Sabrina Danilin, Frédéric Blanc, Eloi Magnin, Jean-François Démonet, Hakan Gurvit, Bruno Dubois, Giovanni B. Frisoni, Eric Schordan, Florence Pasquier, Stéphanie Boutillier, François Sellal, Sami Ait Abbi Nazi, Jean Christophe Bier, Saliha Moussaoui, Audrey Gabelle, Catherine Mutter, Renaud David, and Adrian Ivanoiu

Subjects
Epidemiology, business.industry, Health Policy, Disease, medicine.disease, Bioinformatics, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neuroimaging, medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, business
Published
2020

46. Different abnormalities of electroencephalographic (EEG) markers in quiet wakefulness are related to motor visual hallucinations in patients with Parkinson’s and Lewy body diseases

Author

Giovanni B. Frisoni, Moira Marizzoni, Ian G. McKeith, Dag Aarsland, Raffaele Ferri, Susanna Lopez, Görsev Yener, Lutfu Hanoglu, Gerhard Ransmayr, Maria Teresa Pascarelli, Laura Vacca, Lucia Farotti, Lucilla Parnetti, Carlo de Lena, Andrea Soricelli, Flavio Nobili, Marco Onofrj, Bahar Güntekin, John-Paul Taylor, Raffaella Franciotti, Laura Bonanni, Dario Arnaldi, Maria Francesca De Pandis, Peter Fuhr, Fabrizia D'Antonio, Ute Gschwandtner, Claudio Del Percio, Antonio Ivano Triggiani, Fabrizio Stocchi, Francesco Famà, Harald Hampel, Giuseppe Noce, Roberta Lizio, Derya Durusu Emek-Savaş, and Claudio Babiloni

Subjects
medicine.medical_specialty, medicine.diagnostic_test, Lewy body, Epidemiology, business.industry, Health Policy, Electroencephalography, Audiology, medicine.disease, Visual Hallucination, Quiet wakefulness, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, In patient, Neurology (clinical), Geriatrics and Gerontology, business
Published
2020

47. Bacteria isolated from the stools of Alzheimer’s disease patients exacerbate cognitive impairment in 3xTg AD mouse model

Author

Giovanni B. Frisoni, Marco Salvatore, Peppino Mirabelli, Benjamin B. Tournier, Moira Marizzoni, Arthur Pauis, Annamaria Cattaneo, and Philippe Millet

Subjects
biology, Epidemiology, business.industry, Health Policy, Disease, biology.organism_classification, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Immunology, Medicine, Neurology (clinical), Geriatrics and Gerontology, Cognitive impairment, business, Bacteria
Published
2020

48. Abnormalities of Cortical Sources of Resting State Alpha Electroencephalographic Rhythms are Related to Education Attainment in Cognitively Unimpaired Seniors and Patients with Alzheimer's Disease and Amnesic Mild Cognitive Impairment

Author

Tuba Aktürk, Giovanni B. Frisoni, Claudio Babiloni, Dario Arnaldi, Virginia Cipollini, Laura Vacca, Andrea Soricelli, Bahar Güntekin, Claudio Del Percio, Fabrizio Stocchi, Moira Marizzoni, Giuseppe Noce, Andrea Panzavolta, Ivan Lorenzo, Görsev Yener, Carla Buttinelli, Lutfu Hanoglu, Franco Giubilei, Susanna Lopez, Roberta Lizio, Yağmur Özbek, Flavio Nobili, Raffaele Ferri, Francesco Orzi, and Francesco Famà

Subjects
Male, medicine.medical_specialty, Cognitive Neuroscience, Rest, Alpha (ethology), Neuropathology, Audiology, Neuropsychological Tests, Affect (psychology), Neuroprotection, Cellular and Molecular Neuroscience, Alzheimer Disease, medicine, Humans, Cognitive Dysfunction, Cognitive reserve, Aged, Cerebral Cortex, Resting state fMRI, business.industry, aging, resting state electroencephalographic (rsEEG) rhythms, Neurodegeneration, Neuropsychology, education attainment, exact low-resolution brain electromagnetic source tomography (eLORETA), mild cognitive impairment due to Alzheimer's disease (ADMCI), Electroencephalography, medicine.disease, mild cognitive impairment due to Alzheimer’s disease (ADMCI), Alpha Rhythm, Educational Status, Female, Amnesia, business
Abstract

In normal old (Nold) and Alzheimer’s disease (AD) persons, a high cognitive reserve (CR) makes them more resistant and resilient to brain neuropathology and neurodegeneration. Here, we tested whether these effects may affect neurophysiological oscillatory mechanisms generating dominant resting state electroencephalographic (rsEEG) alpha rhythms in Nold and patients with mild cognitive impairment (MCI) due to AD (ADMCI). Data in 60 Nold and 70 ADMCI participants, stratified in higher (Edu+) and lower (Edu–) educational attainment subgroups, were available in an Italian–Turkish archive. The subgroups were matched for age, gender, and education. RsEEG cortical sources were estimated by eLORETA freeware. As compared to the Nold-Edu– subgroup, the Nold-Edu+ subgroup showed greater alpha source activations topographically widespread. On the contrary, in relation to the ADMCI-Edu– subgroup, the ADMCI-Edu+ subgroup displayed lower alpha source activations topographically widespread. Furthermore, the 2 ADMCI subgroups had matched cerebrospinal AD diagnostic biomarkers, brain gray–white matter measures, and neuropsychological scores. The current findings suggest that a high CR may be related to changes in rsEEG alpha rhythms in Nold and ADMCI persons. These changes may underlie neuroprotective effects in Nold seniors and subtend functional compensatory mechanisms unrelated to brain structure alterations in ADMCI patients.

Published
2020

49. Amygdalar nuclei and hippocampal subfields on MRI

Author

Michela Pievani, Agnese Picco, Jean-Philippe Ranjeva, Giovanni B. Frisoni, Lucilla Parnetti, Piero Floridi, Frederik Barkhof, Jens Wiltfang, Marco Salvatore, Helene Gros-Dagnac, Antonio Ferretti, Julien Sein, Massimo Caulo, Alberto Beltramello, Pierre Payoux, Marco Aiello, Joost P.A. Kuijer, Roberto Tarducci, Tilman Hensch, Renaud Lopes, Björn H. Schott, Peter Schönknecht, Luca Roccatagliata, Camillo Marra, David Bartrés-Faz, Jill C. Richardson, Jorge Jovicich, Flavio Nobili, Antonios Drevelegas, Pieter Jelle Visser, Olivier Blin, Paolo Maria Rossini, Karl Titus Hoffmann, Mira Didic, Régis Bordet, Bernhard W. Müller, Francesca B. Pizzini, Magda Tsolaki, Ute Fiedler, Manos Constantinides, Giulia Quattrini, Moira Marizzoni, Andrea Soricelli, Núria Bargalló, Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia [Brescia], Center for Mind/Brain Sciences, University of Trento, Corso Bettini, 31, 38068, Rovereto, TN, Italy, IRCCS SDN Napoli, Department of Neuroradiology and Image Research Platform, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Department of Radiology and Nuclear Medicine [Amsterdam], VU University Medical Center [Amsterdam], Institute of Neurology, Queen Square, London, Department of Medicine and Health Sciences, Faculty of Medicine, Universitat de Barcelona and IDIBAPS, Barcelona, Department of Radiology, IRCCS 'Sacro Cuore-Don Calabria', Negrar, Verona, Radiology, Department of Diagnostic and Public Health, University of Verona, Verona, Centre investigation clinique - Unité de pharmacologie clinique et d'évaluations thérapeutiques (CIC-UPCET), Assistance Publique - Hôpitaux de Marseille (APHM), Institut de Neurosciences des Systèmes (INS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University 'G. d'Annunzio' of Chieti-Pescara [Chieti], Interbalkan Medical Center of Thessaloniki, LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, Neuroradiology Unit, Perugia General Hospital, Perugia, Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Department of Psychiatry and Psychotherapy, University of Leipzig Medical Center, Leipzig, Department of Neuroradiology, University Hospital Leipzig, LVR-Hospital Essen, Department for Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI), Università degli Studi di Genova, 16132 Genova, Section of Neurology, Department of Medicine, University of Perugia, Perugia, Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), IRCCS, Ospedale Policlinico San Martino, Genova, Italy, Department of Health Science (DISSAL), University of Genoa, Genoa, Dept. Neuroscience & Rehabilitation, IRCCS San Raffaele-Pisana, Rome, Department of Psychiatry and Psychotherapy, University Medical Center Goettingen (UMG), Göttingen, Leibniz Institute for Neurobiology, Magdeburg, Center for Neurodegenerative Diseases (DZNE), Goettingen, Medical Physics Unit, Perugia General Hospital, Perugia, Aristotle University of Thessaloniki, Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, Netherlands, Maastricht University, Maastricht, Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, German Center for Neurodegenerative Diseases (DZNE), Goettingen, GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), Laboratory of Neuroimaging of aging, Memory clinic and LANVIE, Geneva University Hospital and Geneva University, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Amsterdam Neuroscience - Brain Imaging, Radiology and nuclear medicine, Neurology, Università degli Studi di Brescia = University of Brescia (UniBs), Università degli Studi di Trento (UNITN), Università degli studi di Verona = University of Verona (UNIVR), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lille Neurosciences & Cognition - U 1172 (LilNCog), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Leipzig University, Università degli studi di Genova = University of Genoa (UniGe), Università degli Studi di Perugia = University of Perugia (UNIPG), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), and Leibniz Institute for Neurobiology [Magdeburg] (LIN)

Subjects
Male, STRUCTURAL DIFFERENCES, Neurology, genetic structures, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, FreeSurfer, Medizin, Hippocampus, Hippocampal formation, Amygdalar nuclei, Hippocampal subfields, Multicenter MRI study, Reliability analysis, 0302 clinical medicine, methods [Magnetic Resonance Imaging], hippocampal subfields, multicenter MRI study, reliability analysis, methods [Image Processing, Computer-Assisted], Image Processing, Computer-Assisted, METHODS FREESURFER, ELDERLY-PATIENTS, ComputingMilieux_MISCELLANEOUS, 05 social sciences, Subiculum, BORDERLINE PERSONALITY-DISORDER, Middle Aged, Amygdala, HUMAN BRAIN, Magnetic Resonance Imaging, ALZHEIMERS-DISEASE, standards [Image Processing, Computer-Assisted], Settore MED/26 - NEUROLOGIA, MANUAL SEGMENTATION, medicine.anatomical_structure, Brain size, Cohort, Female, methods [Neuroimaging], Adult, medicine.medical_specialty, Cognitive Neuroscience, anatomy & histology [Hippocampus], Neuroimaging, Cognitive neuroscience, SURFACE-BASED ANALYSIS, 050105 experimental psychology, lcsh:RC321-571, 03 medical and health sciences, medicine, Humans, 0501 psychology and cognitive sciences, ddc:610, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Aged, standards [Magnetic Resonance Imaging], business.industry, Reproducibility of Results, SAMPLE-SIZE CALCULATIONS, ddc:616.8, nervous system, anatomy & histology [Amygdala], Nuclear medicine, business, 030217 neurology & neurosurgery, standards [Neuroimaging], Software, FUNCTIONAL-ORGANIZATION
Abstract

Background: The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults.Methods: Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1-90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (epsilon) and spatial overlapping coefficient (DICE) between test and retest session.Results: Significant MRI site and vendor effects (p 0.43, p 0.80).Conclusion: Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials.

Published
2020

50. CSF cutoffs for MCI due to AD depend on APOEε4 carrier status

Author

Jean-Philippe Ranjeva, Frederik Barkhof, Jorge Jovicich, Régis Bordet, Jill C. Richardson, Elena Rolandi, Magda Tsolaki, Andrea Soricelli, Olivier Blin, Lucilla Parnetti, Marco Salvatore, Claudio Babiloni, Tilman Hensch, Jens Wiltfang, Camillo Marra, José Luis Molinuevo, Libera Cavaliere, Samantha Galluzzi, Moira Marizzoni, Diego Albani, Mira Didic, Clarissa Ferrari, Flavio Nobili, Federica Fusco, Paolo Maria Rossini, Giovanni B. Frisoni, Gianluigi Forloni, Federica Ribaldi, Pierre Payoux, Pieter Jelle Visser, Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia [Brescia], Department of Physiology and Pharmacology 'Vittorio Erspamer', Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Neuroscience Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milano, Department of Radiology and Nuclear Medicine [Amsterdam], VU University Medical Center [Amsterdam], Institutes of Neurology and Healthcare Engineering, UCL, London, Institut de Neurosciences des Systèmes (INS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Department of Psychiatry and Psychotherapy, University of Leipzig Medical Center, Leipzig, Center for Mind/Brain Sciences, University of Trento, Corso Bettini, 31, 38068, Rovereto, TN, Italy, Department of Gerontology, Neurosciences & Orthopedics, Catholic University, Rome, Alzheimer's Disease Unit and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Dipartimento di Neuroscienze, riabilitazione, oftalmologia, genetica e scienze materno-infantili [Genova] (DINOGMI), Universita degli studi di Genova, Section of Neurology, Centre for Memory Disturbances, University of Perugia, Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Area Neuroscience, IRCCS San Raffaele, Rome, IRCCS SDN Napoli, Department of Neurology (Aristotle University of Thessaloniki), Aristotle University of Thessaloniki, Alzheimer Center Amsterdam, LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre investigation clinique - Unité de pharmacologie clinique et d'évaluations thérapeutiques (CIC-UPCET), Assistance Publique - Hôpitaux de Marseille (APHM), Laboratory of Neuroimaging of aging, Memory clinic and LANVIE, Geneva University Hospital and Geneva University, Amsterdam Neuroscience - Neurodegeneration, Radiology and nuclear medicine, Università degli Studi di Brescia = University of Brescia (UniBs), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Leipzig University, Università degli Studi di Trento (UNITN), Università degli studi di Genova = University of Genoa (UniGe), Università degli Studi di Perugia = University of Perugia (UNIPG), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), and Lille Neurosciences & Cognition - U 1172 (LilNCog)

Subjects
Male, 0301 basic medicine, Oncology, Apolipoprotein E, Aging, Medizin, Cohort Studies, 0302 clinical medicine, Cerebrospinal fluid, Cutoff, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, biology, General Neuroscience, Alzheimer's disease, 3. Good health, Settore MED/26 - NEUROLOGIA, Biomarker (medicine), Female, Heterozygote, medicine.medical_specialty, CSF cutoff, Disease progression, Mild cognitive impairment, Tau protein, tau Proteins, 03 medical and health sciences, Apolipoproteins E, Neuroimaging, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, Cognitive Dysfunction, Aged, Amyloid beta-Peptides, Receiver operating characteristic, business.industry, medicine.disease, Peptide Fragments, ddc:616.8, 030104 developmental biology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, biology.protein, Neurology (clinical), Geriatrics and Gerontology, business, Biomarkers, 030217 neurology & neurosurgery, Developmental Biology
Abstract

Amyloid and tau pathological accumulation should be considered for Alzheimer's disease (AD) definition and before subjects' enrollment in disease-modifying trials. Although age, APOEε4, and sex influence cerebrospinal fluid (CSF) biomarker levels, none of these variables are considered by current normality/abnormality cutoffs. Using baseline CSF data from 2 independent cohorts (PharmaCOG/European Alzheimer's Disease Neuroimaging Initiative and Alzheimer's Disease Neuroimaging Initiative), we investigated the effect of age, APOEε4 status, and sex on CSF Aβ42/P-tau distribution and cutoff extraction by applying mixture models with covariates. The Aβ42/P-tau distribution revealed the presence of 3 subgroups (AD-like, intermediate, control-like) and 2 cutoffs. The identification of the intermediate subgroup and of the higher cutoff was APOEε4 dependent in both cohorts. APOE-specific classification (higher cutoff for APOEε4+, lower cutoff for APOEε4-) showed higher diagnostic accuracy in identifying MCI due to AD compared to single Aβ42 and Aβ42/P-tau cutoffs. APOEε4 influences amyloid and tau CSF markers and AD progression in MCI patients supporting i) the use of APOE-specific cutoffs to identify MCI due to AD and ii) the utility of considering APOE genotype for early AD diagnosis.

Published
2020

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