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1. Association of plasma YKL-40 with brain amyloid-β levels, memory performance, and sex in subjective memory complainers

Author

Andrea Vergallo, Simone Lista, Pablo Lemercier, Patrizia A. Chiesa, Henrik Zetterberg, Kaj Blennow, Marie-Claude Potier, Marie-Odile Habert, Filippo Baldacci, Enrica Cavedo, Filippo Caraci, Bruno Dubois, Harald Hampel, Hovagim Bakardjian, Habib Benali, Hugo Bertin, Joel Bonheur, Laurie Boukadida, Nadia Boukerrou, Patrizia Chiesa, Olivier Colliot, Marion Dubois, Stéphane Epelbaum, Geoffroy Gagliardi, Remy Genthon, Marion Houot, Aurélie Kas, Foudil Lamari, Marcel Levy, Christiane Metzinger, Fanny Mochel, Francis Nyasse, Catherine Poisson, Marie Revillon, Antonio Santos, Katia Santos Andrade, Marine Sole, Mohmed Surtee, Michel Thiebaut de Schotten, Nadjia Younsi, Mohammad Afshar, Lisi Flores Aguilar, Leyla Akman-Anderson, Joaquín Arenas, Jesús Ávila, Claudio Babiloni, Richard Batrla, Norbert Benda, Keith L. Black, Arun L.W. Bokde, Ubaldo Bonuccelli, Karl Broich, Francesco Cacciola, Giuseppe Caruso, Juan Castrillo†, Roberto Ceravolo, Massimo Corbo, Jean-Christophe Corvol, Augusto Claudio Cuello, Jeffrey L. Cummings, Herman Depypere, Andrea Duggento, Enzo Emanuele, Valentina Escott-Price, Howard Federoff, Maria Teresa Ferretti, Massimo Fiandaca, Richard A. Frank, Francesco Garaci, Hugo Geerts, Ezio Giacobini, Filippo S. Giorgi, Edward J. Goetzl, Manuela Graziani, Marion Haberkamp, Britta Hänisch, Karl Herholz, Felix Hernandez, Bruno P. Imbimbo, Dimitrios Kapogiannis, Eric Karran, Steven J. Kiddle, Seung H. Kim, Yosef Koronyo, Maya Koronyo-Hamaoui, Todd Langevin, Stéphane Lehéricy, Francisco Llavero, Jean Lorenceau, Alejandro Lucía, Dalila Mango, Mark Mapstone, Christian Neri, Robert Nisticò, Sid E. O’bryant, Giovanni Palermo, George Perry, Craig Ritchie, Simone Rossi, Amira Saidi, Emiliano Santarnecchi, Lon S. Schneider, Olaf Sporns, Nicola Toschi, Pedro L. Valenzuela, Bruno Vellas, Steven R. Verdooner, Nicolas Villain, Kelly Virecoulon Giudici, Mark Watling, Lindsay A. Welikovitch, Janet Woodcock, Erfan Younesi, José L. Zugaza, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Biomédicale (LIB), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
musculoskeletal diseases, 0301 basic medicine, Apolipoprotein E, Male, Risk, Aging, medicine.medical_specialty, Amyloid, YKL-40, [SDV]Life Sciences [q-bio], Disease, 03 medical and health sciences, Alzheimer's disease, amyloid, neuroinflammation, Sex, 0302 clinical medicine, Neuroinflammation, Alzheimer Disease, Memory, Internal medicine, medicine, Premovement neuronal activity, Humans, Effects of sleep deprivation on cognitive performance, Chitinase-3-Like Protein 1, Longitudinal Studies, Inflammation, Amyloid beta-Peptides, business.industry, General Neuroscience, Neurodegeneration, Settore FIS/07, Brain, medicine.disease, 030104 developmental biology, Endocrinology, Biomarker (medicine), Female, Neurology (clinical), Geriatrics and Gerontology, business, Alzheimer’s disease, 030217 neurology & neurosurgery, Biomarkers, Developmental Biology
Abstract

Neuroinflammation, a key early pathomechanistic alteration of Alzheimer’s disease, may represent either a detrimental or a compensatory mechanism or both (according to the disease stage). YKL-40, a glycoprotein highly expressed in differentiated glial cells, is a candidate biomarker for in vivo tracking neuroinflammation in humans. We performed a longitudinal study in a monocentric cohort of cognitively healthy individuals at risk for Alzheimer’s disease exploring whether age, sex, and the apolipoprotein E e4 allele affect plasma YKL-40 concentrations. We investigated whether YKL-40 is associated with brain amyloid-β (Aβ) deposition, neuronal activity, and neurodegeneration as assessed via neuroimaging biomarkers. Finally, we investigated whether YKL-40 may predict cognitive performance. We found an age-associated increase of YKL-40 and observed that men display higher concentrations than women, indicating a potential sexual dimorphism. Moreover, YKL-40 was positively associated with memory performance and negatively associated with brain Aβ deposition (but not with metabolic signal). Consistent with translational studies, our results suggest a potentially protective effect of glia on incipient brain Aβ accumulation and neuronal homeostasis.

Published
2020

2. Plasma amyloid β 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease

Author

Geoffroy Gagliardi, Roberto Ceravolo, Herman Depypere, Bruno Dubois, Fanny Mochel, Christiane Metzinger, George L. W. Perry, Marine Sole, Massimo S. Fiandaca, Amira Saidi, E. Cavedo, Patrizia Andrea Chiesa, Thiebaud de Schotten M, Juan I. Castrillo, Jean Lorenceau, Jeffrey L. Cummings, Craig W. Ritchie, Ubaldo Bonuccelli, Francesco Cacciola, Arun L.W. Bokde, F. Lamari, Keith L. Black, Marion Haberkamp, Jean-Christophe Corvol, Ann De Vos, Maya Koronyo-Hamaoui, Filippo Sean Giorgi, Todd Langevin, H. Hampel, Richard Frank, Stéphane Epelbaum, Mohmed Surtee, Remy Genthon, Nadjia Younsi, Olaf Sporns, Harald Hampel, Marion Dubois, Filippo Baldacci, Lindsay A. Welikovitch, Karl Broich, Stéphane Lehéricy, Henrik Zetterberg, M.O. Habert, Manuela Graziani, Janet Woodcock, S. Lista, Aurélie Kas, Lon S. Schneider, Katia Andrade, Robert Nisticò, Simone Rossi, Foudil Lamari, Howard J. Federoff, Francis Nyasse, Enrica Cavedo, Lisi Flores Aguilar, Erfan Younesi, M.C. Potier, Seung Hyun Kim, Karl Herholz, Nadia Boukerrou, Lucile Megret, Catherine Poisson, Claudio Babiloni, A.C. Cuello, Dalila Mango, Antonio Melo dos Santos, Norbert Benda, Marcel Levy, A. Vergallo, Patrizia A. Chiesa, Sid E. O'Bryant, Marie Revillon, Nicola Toschi, Hugo Geerts, Maria Teresa Ferretti, Mark Mapstone, Kaj Blennow, Eugeen Vanmechelen, Simone Lista, Marie-Odile Habert, Marie-Claude Potier, Eric Karran, Nicolas Villain, Laurie Boukadida, Emiliano Santarnecchi, Yosef Koronyo, Olivier Colliot, Habib Benali, Hugo Bertin, Valentina Escott-Price, Andrea Duggento, Steven Verdooner, Andrea Vergallo, Christian Neri, Joel Bonheur, Francesco Garaci, Hovagim Bakardjian, Marion Houot, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Biomédicale (LIB), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, Apolipoprotein E, Oncology, Epidemiology, [SDV]Life Sciences [q-bio], Simoa immunoassay, Disease, Cohort Studies, Classification and regression trees (CART), Cognition, 0302 clinical medicine, medicine.diagnostic_test, Health Policy, Amyloidosis, Settore FIS/07, Brain, Alzheimer's disease, 3. Good health, Psychiatry and Mental health, Positron emission tomography, Cohort, Female, Amyloid PET, Machine learning, Plasma amyloid β, Subjective memory complainers, medicine.medical_specialty, 03 medical and health sciences, Cellular and Molecular Neuroscience, Developmental Neuroscience, Alzheimer Disease, Memory, Internal medicine, medicine, Humans, Aged, Amyloid beta-Peptides, Receiver operating characteristic, business.industry, Clinical study design, medicine.disease, Peptide Fragments, Clinical trial, Cerebral Amyloid Angiopathy, 030104 developmental biology, Positron-Emission Tomography, Neurology (clinical), Geriatrics and Gerontology, business, Biomarkers, 030217 neurology & neurosurgery
Abstract

Introduction Blood-based biomarkers of pathophysiological brain amyloid β (Aβ) accumulation, particularly for preclinical target and large-scale interventions, are warranted to effectively enrich Alzheimer's disease clinical trials and management. Methods We investigated whether plasma concentrations of the Aβ 1–40 /Aβ 1–42 ratio, assessed using the single-molecule array (Simoa) immunoassay, may predict brain Aβ positron emission tomography status in a large-scale longitudinal monocentric cohort (N = 276) of older individuals with subjective memory complaints. We performed a hypothesis-driven investigation followed by a no-a-priori hypothesis study using machine learning. Results The receiver operating characteristic curve and machine learning showed a balanced accuracy of 76.5% and 81%, respectively, for the plasma Aβ 1–40 /Aβ 1–42 ratio. The accuracy is not affected by the apolipoprotein E ( APOE ) e4 allele, sex, or age. Discussion Our results encourage an independent validation cohort study to confirm the indication that the plasma Aβ 1–40 /Aβ 1–42 ratio, assessed via Simoa, may improve future standard of care and clinical trial design.

Published
2019

3. O3‐12‐04: THE NEURONAL COMPENSATION MODEL OF THE PRECLINICAL STAGE OF ALZHEIMER'S DISEASE: RESULTS FROM THE INSIGHT‐PRE AD STUDY

Author

Harald Hampel, Stéphane Epelbaum, Bruno Dubois, Olivier Colliot, Anne Bertrand, Marie-Odile Habert, Geoffroy Gagliardi, Marion Houot, Jean-François Mangin, Marie-Claude Potier, Francis Nyasse, Foudil Lamari, Hovagim Bakardjian, Federica Cacciamani, and Simone Lista

Subjects
Epidemiology, business.industry, Health Policy, Disease, Compensation (engineering), Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Neurology (clinical), Geriatrics and Gerontology, Preclinical stage, business, Neuroscience
Published
2018

4. Cognitive and neuroimaging features and brain β-amyloidosis in individuals at risk of Alzheimer's disease (INSIGHT-preAD): a longitudinal observational study

Author

Foudil Lamari, Marion Houot, Habib Benali, Fanny Mochel, Christiane Metzinger, Catherine Poisson, Stéphane Epelbaum, Marcel Levy, Valentina La Corte, Claire Letondor, Agnès Michon, Geoffroy Gagliardi, Francis Nyasse, Pauline Glasman, Marie-Claude Potier, Filippo Baldacci, Valérie Simon, Alexis Genin, Olga Uspenskaya, Juliette Ly, Gaëlle Fontaine, Simone Lista, Bruno Dubois, Maya Kilani, Enrica Cavedo, Nadjia Younsi, Caroline Tandetnik, Jean-François Mangin, Alexandra Auffret, Rachel Schindler, Marie-Odile Habert, Katia Santos-Andrade, Marine Sole, Antonio Melo dos Santos, Marion Dubois, Aurélie Kas, Anne Bertrand, Katrine Rojkova, Laurie Boukadida, Marie Revillon, Laure Seux, Stanley Durrleman, Marc Teichmann, Harald Hampel, Olivier Colliot, Stephie Ratovohery, Remy Genthon, Navichka Jungalee, Federica Cacciamani, Michel Thiebaut de Shotten, Ismahane Benakki, Patrizia A. Chiesa, Perrine Roy, Hovagim Bakardjian, Ornella Makiese, Luce Dauphinot, Christelle Audrain, Hugo Bertin, Mark Lowrey, Stéphane Lehéricy, Centre des Maladies Cognitives et Comportementales [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), IQVIA, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Clinical Dementia Rating, Brain Structure and Function, Neuroimaging, Neuropsychological Tests, 03 medical and health sciences, 0302 clinical medicine, Cognition, Functional neuroimaging, Alzheimer Disease, Risk Factors, Internal medicine, medicine, Humans, Longitudinal Studies, Cognitive decline, Aged, Aged, 80 and over, Amyloid beta-Peptides, business.industry, Amyloidosis, [SCCO.NEUR]Cognitive science/Neuroscience, Neuropsychology, Brain, Actigraphy, medicine.disease, Magnetic Resonance Imaging, 3. Good health, 030104 developmental biology, Positron-Emission Tomography, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Executive dysfunction
Abstract

For the INSIGHT-preAD study group; International audience; Improved understanding is needed of risk factors and markers of disease progression in preclinical Alzheimer's disease. We assessed associations between brain β-amyloidosis and various cognitive and neuroimaging parameters with progression of cognitive decline in individuals with preclinical Alzheimer's disease.The INSIGHT-preAD is an ongoing single-centre observational study at the Salpêtrière Hospital, Paris, France. Eligible participants were age 70–85 years with subjective memory complaints but unimpaired cognition and memory (Mini-Mental State Examination [MMSE] score ≥27, Clinical Dementia Rating score 0, and Free and Cued Selective Reminding Test [FCSRT] total recall score ≥41). We stratified participants by brain amyloid β deposition on 18F-florbetapir PET (positive or negative) at baseline. All patients underwent baseline assessments of demographic, cognitive, and psychobehavioural, characteristics, APOE ε4 allele carrier status, brain structure and function on MRI, brain glucose-metabolism on 18F-fluorodeoxyglucose (18F-FDG) PET, and event-related potentials on electroencephalograms (EEGs). Actigraphy and CSF investigations were optional. Participants were followed up with clinical, cognitive, and psychobehavioural assessments every 6 months, neuropsychological assessments, EEG, and actigraphy every 12 months, and MRI, and 18F-FDG and 18F-florbetapir PET every 24 months. We assessed associations of amyloid β deposition status with test outcomes at baseline and 24 months, and with clinical status at 30 months. Progression to prodromal Alzheimer's disease was defined as an amnestic syndrome of the hippocampal type From May 25, 2013, to Jan 20, 2015, we enrolled 318 participants with a mean age of 76·0 years (SD 3·5). The mean baseline MMSE score was 28·67 (SD 0·96), and the mean level of education was high (score >6 [SD 2] on a scale of 1–8, where 1=infant school and 8=higher education). 88 (28%) of 318 participants showed amyloid β deposition and the remainder did not. The amyloid β subgroups did not differ for any psychobehavioural, cognitive, actigraphy, and structural and functional neuroimaging results after adjustment for age, sex, and level of education More participants positive for amyloid β deposition had the APOE ε4 allele (33 [38%] vs 29 [13%], p

Published
2018

5. P3‐165: Plasma Biomarker Profile of Amyloid, TAU, and Neuronal Pathophysiology in Cognitively Normal Preclinical Individuals Stratified by Amyloid‐Pet Status

Author

Hovagim Bakardjian, Foudil Lamari, Marie-Odile Habert, Bruno Dubois, Kaj Blennow, Simone Lista, Harald Hampel, Henrik Zetterberg, and Francis Nyasse

Subjects
Pathology, medicine.medical_specialty, Amyloid, Epidemiology, business.industry, Health Policy, Amyloid pet, Pathophysiology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Biomarker (medicine), Neurology (clinical), Geriatrics and Gerontology, business
Published
2016

6. P4‐111: Alzheimer's Disease Detection at the Preclinical Stage Using a Novel SNP Genotyping Array

Author

Julie Davis, Harald Hampel, John Hardy, Francis Nyasse, Geoff Scopes, Claire Bloor, Maryam Shoai, Valentina Escott-Price, Bruno Dubois, Simon M. Laws, Simone Lista, Lakshmi Radhakrishnan, Marie-Claude Potier, Hovagim Bakardjian, and Richard Pither

Subjects
Disease detection, Epidemiology, business.industry, Health Policy, Computational biology, SNP genotyping, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Neurology (clinical), Geriatrics and Gerontology, business, Preclinical stage
Published
2016

7. P2‐151: Cerebrospinal Fluid Biomarker Profile of Amyloid, TAU, Synaptic, Microglial, and Lysosomal Pathophysiology in Cognitively Normal Preclinical Individuals Stratified by Amyloid‐Pet Status

Author

Hovagim Bakardjian, Harald Hampel, Henrik Zetterberg, Simone Lista, Francis Nyasse, Marie-Odile Habert, Bruno Dubois, Foudil Lamari, and Kaj Blennow

Subjects
Pathology, medicine.medical_specialty, Amyloid, Epidemiology, business.industry, Health Policy, Amyloid pet, Pathophysiology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Cerebrospinal fluid, Developmental Neuroscience, Medicine, Biomarker (medicine), Neurology (clinical), Geriatrics and Gerontology, business
Published
2016

8. O4‐02‐03: Insight‐Ad Study: A Monocentric Cohort for the Study of the Preclinical Stage of Alzheimer's Disease

Author

Bruno Dubois, Stéphane Epelbaum, Francis Nyasse, Harald Hampel, Olivier Colliot, Habib Benali, Hova Bakardjian, Simone Lista, Marie-Odile Habert, Marie-Claude Potier, and Foudil Lamari

Subjects
Oncology, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Internal medicine, Cohort, medicine, Neurology (clinical), Geriatrics and Gerontology, business, Preclinical stage
Published
2016

9. Biomarker-guided clustering of Alzheimer's disease clinical syndromes

Author

Toschi, Nicola, Lista, Simone, Lamari, Foudil, Genthon, Remy, Habert, Marie-Odile, Dubois, Bruno, Floris, Roberto, Garaci, Francesco, Vergallo, Andrea, Hampel, Harald, group, INSIGHT-preAD study, Initiative, Alzheimer Precision Medicine, Baldacci, Filippo, Bakardjian, Hovagim, Benali, Habib, Bertin, Hugo, Bonheur, Joel, Boukadida, Laurie, Boukerrou, Nadia, Cavedo, Enrica, Chiesa, Patrizia, Colliot, Olivier, Dubois, Marion, Epelbaum, Stéphane, Gagliardi, Geoffroy, Houot, Marion, Kas, Aurélie, Levy, Marcel, Zetterberg, Henrik, Metzinger, Christiane, Mochel, Fanny, Nyasse, Francis, Poisson, Catherine, Potier, Marie-Claude, Revillon, Marie, Santos, Antonio, Andrade, Katia Santos, Sole, Marine, Blennow, Kaj, Surtee, Mohmed, Thiebaut de Schotten, Michel, Younsi, Nadjia, Kilimann, Ingo, Teipel, Stefan J, Melo Dos Santos, Antonio, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CCSD, Accord Elsevier, Università degli Studi di Roma Tor Vergata [Roma], Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), University of Pisa - Università di Pisa, University of Gothenburg (GU), University of Rostock, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre pour l'Acquisition et le Traitement des Images (CATI), Eisai, and Hovagim Bakardjian, Habib Benali, Hugo Bertin, Joel Bonheur, Laurie Boukadida, Nadia Boukerrou, Enrica Cavedo, Patrizia Chiesa, Olivier Colliot, Bruno Dubois, Marion Dubois, Stéphane Epelbaum, Geoffroy Gagliardi, Remy Genthon, Marie-Odile Habert, Harald Hampel, Marion Houot, Aurélie Kas, Foudil Lamari, Marcel Levy, Simone Lista, Christiane Metzinger, Fanny Mochel, Francis Nyasse, Catherine Poisson, Marie-Claude Potier, Marie Revillon, Antonio Santos, Katia Santos Andrade, Marine Sole, Mohmed Surtee, Michel Thiebaut de Schotten, Andrea Vergallo, Nadjia Younsi

Subjects
Male, 0301 basic medicine, Oncology, Aging, [SDV]Life Sciences [q-bio], cerebrospinal fluid [Amyloid beta-Peptides], Disease, 0302 clinical medicine, Risk Factors, General Neuroscience, Precision medicine, diagnosis [Alzheimer Disease], Alzheimer's disease, Middle Aged, Pathophysiology, 3. Good health, [SDV] Life Sciences [q-bio], cerebrospinal fluid [Alzheimer Disease], cerebrospinal fluid [Cognitive Dysfunction], cerebrospinal fluid [Biomarkers], Biomarker (medicine), Female, Biomarker-guided categorization, Clustering, medicine.medical_specialty, tau Proteins, Neuropathology, 03 medical and health sciences, Settore MED/36 - Diagnostica per Immagini e Radioterapia, Alzheimer Disease, Internal medicine, medicine, Humans, Dementia, Cognitive Dysfunction, ddc:610, cerebrospinal fluid [Peptide Fragments], Cluster analysis, Aged, Amyloid beta-Peptides, business.industry, medicine.disease, Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin), Peptide Fragments, 030104 developmental biology, diagnosis [Cognitive Dysfunction], cerebrospinal fluid [tau Proteins], Spatial clustering, Neurology (clinical), Geriatrics and Gerontology, business, Biomarkers, 030217 neurology & neurosurgery, Developmental Biology
Abstract

International audience; Alzheimer's disease (AD) neuropathology is extremely heterogeneous, and the evolution from preclinical to mild cognitive impairment until dementia is driven by interacting genetic/biological mechanisms not fully captured by current clinical/research criteria. We characterized the heterogeneous "construct" of AD through a cerebrospinal fluid biomarker-guided stratification approach. We analyzed 5 validated pathophysiological cerebrospinal fluid biomarkers (Aβ1-42, t-tau, p-tau181, NFL, YKL-40) in 113 participants (healthy controls [N = 20], subjective memory complainers [N = 36], mild cognitive impairment [N = 20], and AD dementia [N = 37], age: 66.7 ± 10.4, 70.4 ± 7.7, 71.7 ± 8.4, 76.2 ± 3.5 years [mean ± SD], respectively) using Density-Based Spatial Clustering of Applications with Noise, which does not require a priori determination of the number of clusters. We found 5 distinct clusters (sizes: N = 38, 16, 24, 14, and 21) whose composition was independent of phenotypical groups. Two clusters showed biomarker profiles linked to neurodegenerative processes not associated with classical AD-related pathophysiology. One cluster was characterized by the neuroinflammation biomarker YKL-40. Combining nonlinear data aggregation with informative biomarkers can generate novel patient strata which are representative of cellular/molecular pathophysiology and may aid in predicting disease evolution and mechanistic drug response.

Published
2019

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