7 results on '"Chamoun, Mira"'
Search Results
2. Stage-specific links between plasma neurofilament light and imaging biomarkers of Alzheimer's disease.
- Author
-
Benedet AL, Leuzy A, Pascoal TA, Ashton NJ, Mathotaarachchi S, Savard M, Therriault J, Kang MS, Chamoun M, Schöll M, Zimmer ER, Gauthier S, Labbe A, Zetterberg H, Rosa-Neto P, and Blennow K
- Subjects
- Aged, Aged, 80 and over, Aging psychology, Amyloid beta-Peptides blood, Apolipoprotein E4 genetics, Cognitive Dysfunction blood, Cognitive Dysfunction diagnostic imaging, Cohort Studies, Cross-Sectional Studies, Disease Progression, Female, Gray Matter diagnostic imaging, Humans, Magnetic Resonance Imaging, Male, Positron-Emission Tomography, White Matter diagnostic imaging, tau Proteins blood, Alzheimer Disease blood, Alzheimer Disease diagnostic imaging, Biomarkers blood, Neurofilament Proteins blood
- Abstract
Neurofilament light (NfL) is a marker of neuroaxonal injury, a prominent feature of Alzheimer's disease. It remains uncertain, however, how it relates to amyloid and tau pathology or neurodegeneration across the Alzheimer's disease continuum. The aim of this study was to investigate how plasma NfL relates to amyloid and tau PET and MRI measures of brain atrophy in participants with and without cognitive impairment. We retrospectively examined the association between plasma NfL and MRI measures of grey/white matter volumes in the Alzheimer's Disease Neuroimaging Initiative [ADNI: n = 1149; 382 cognitively unimpaired control subjects and 767 cognitively impaired participants (mild cognitive impairment n = 420, Alzheimer's disease dementia n = 347)]. Longitudinal plasma NfL was measured using single molecule array (Simoa) technology. Cross-sectional associations between plasma NfL and PET amyloid and tau measures were independently assessed in two cohorts: ADNI [n = 198; 110 cognitively unimpaired, 88 cognitively impaired (MCI n = 67, Alzheimer's disease dementia n = 21), data accessed October 2018]; and Translational Biomarkers in Aging and Dementia [TRIAD, n = 116; 74 cognitively unimpaired, 42 cognitively impaired (MCI n = 16, Alzheimer's disease dementia n = 26), data obtained November 2017 to January 2019]. Associations between plasma NfL and imaging-derived measures were examined voxel-wise using linear regression (cross-sectional) and linear mixed effect models (longitudinal). Cross-sectional analyses in both cohorts showed that plasma NfL was associated with PET findings in brain regions typically affected by Alzheimer's disease; associations were specific to amyloid PET in cognitively unimpaired and tau PET in cognitively impaired (P < 0.05). Longitudinal analyses showed that NfL levels were associated with grey/white matter volume loss; grey matter atrophy in cognitively unimpaired was specific to APOE ε4 carriers (P < 0.05). These findings suggest that plasma NfL increases in response to amyloid-related neuronal injury in preclinical stages of Alzheimer's disease, but is related to tau-mediated neurodegeneration in symptomatic patients. As such, plasma NfL may a useful measure to monitor effects in disease-modifying drug trials., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
- Full Text
- View/download PDF
3. Mild behavioral impairment is associated with β-amyloid but not tau or neurodegeneration in cognitively intact elderly individuals.
- Author
-
Lussier FZ, Pascoal TA, Chamoun M, Therriault J, Tissot C, Savard M, Kang MS, Mathotaarachchi S, Benedet AL, Parsons M, Qureshi MNI, Thomas ÉM, Shin M, Dion LA, Massarweh G, Soucy JP, Tsai IH, Vitali P, Ismail Z, Rosa-Neto P, and Gauthier S
- Subjects
- Aged, Brain metabolism, Female, Humans, Magnetic Resonance Imaging, Male, Positron-Emission Tomography, Amyloid metabolism, Biomarkers, Healthy Volunteers statistics & numerical data, Image Processing, Computer-Assisted statistics & numerical data, tau Proteins metabolism
- Abstract
Introduction: Mild behavioral impairment (MBI) is characterized by the emergence of neuropsychiatric symptoms in elderly persons. Here, we examine the associations between MBI and Alzheimer's disease (AD) biomarkers in asymptomatic elderly individuals., Methods: Ninety-six cognitively normal elderly individuals underwent MRI, [
18 F]AZD4694 β-amyloid-PET, and [18 F]MK6240 tau-PET. MBI was assessed using the MBI Checklist (MBI-C). Pearson's correlations and voxel-based regressions were used to evaluate the relationship between MBI-C score and [18 F]AZD4694 retention, [18 F]MK6240 retention, and gray matter (GM) volume., Results: Pearson correlations revealed a positive relationship between MBI-C score and global and striatal [18 F]AZD4694 standardized uptake value ratios (SUVRs). Voxel-based regression analyses revealed a positive correlation between MBI-C score and [18 F]AZD4694 retention. No significant correlations were found between MBI-C score and [18 F]MK6240 retention or GM volume., Conclusion: We demonstrate for the first time a link between MBI and early AD pathology in a cognitively intact elderly population, supporting the use of the MBI-C as a metric to enhance clinical trial enrolment., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)- Published
- 2020
- Full Text
- View/download PDF
4. Quantification of SNAP-25 with mass spectrometry and Simoa: a method comparison in Alzheimer’s disease
- Author
-
Nilsson, Johanna, Ashton, Nicholas J., Benedet, Andrea L., Montoliu-Gaya, Laia, Gobom, Johan, Pascoal, Tharick A., Chamoun, Mira, Portelius, Erik, Jeromin, Andreas, Mendes, Muriel, Zetterberg, Henrik, Rosa-Neto, Pedro, Brinkmalm, Ann, and Blennow, Kaj
- Published
- 2022
- Full Text
- View/download PDF
5. Plasma and CSF concentrations of N‐terminal tau fragments associate with in vivo neurofibrillary tangle burden.
- Author
-
Lantero‐Rodriguez, Juan, Tissot, Cécile, Snellman, Anniina, Servaes, Stijn, Benedet, Andrea L., Rahmouni, Nesrine, Montoliu‐Gaya, Laia, Therriault, Joseph, Brum, Wagner S., Stevenson, Jenna, Lussier, Firoza Z., Bezgin, Gleb, Macedo, Arthur C., Chamoun, Mira, Mathotaarachi, Sulantha S., Pascoal, Tharick A., Ashton, Nicholas J., Zetterberg, Henrik, Neto, Pedro Rosa, and Blennow, Kaj
- Abstract
INTRODUCTION: Fluid biomarkers capable of specifically tracking tau tangle pathology in vivo are greatly needed. METHODS: We measured cerebrospinal fluid (CSF) and plasma concentrations of N‐terminal tau fragments (NTA‐tau), using a novel immunoassay (NTA) in the TRIAD cohort, consisting of 272 individuals assessed with amyloid beta (Aβ) positron emission tomography (PET), tau PET, magnetic resonance imaging (MRI) and cognitive assessments. RESULTS: CSF and plasma NTA‐tau concentrations were specifically increased in cognitively impaired Aβ‐positive groups. CSF and plasma NTA‐tau concentrations displayed stronger correlations with tau PET than with Aβ PET and MRI, both in global uptake and at the voxel level. Regression models demonstrated that both CSF and plasma NTA‐tau are preferentially associated with tau pathology. Moreover, plasma NTA‐tau was associated with longitudinal tau PET accumulation across the aging and Alzheimer's disease (AD) spectrum. DISCUSSION: NTA‐tau is a biomarker closely associated with in vivo tau deposition in the AD continuum and has potential as a tau tangle biomarker in clinical settings and trials. Highlights: An assay for detecting N‐terminal tau fragments (NTA‐tau) in plasma and CSF was evaluated.NTA‐tau is more closely associated with tau PET than amyloid PET or neurodegeneration.NTA‐tau can successfully track in vivo tau deposition across the AD continuum.Plasma NTA‐tau increased over time only in cognitively impaired amyloid‐β positive individuals. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
6. Differences Between Plasma and Cerebrospinal Fluid Glial Fibrillary Acidic Protein Levels Across the Alzheimer Disease Continuum
- Author
-
Benedet, Andréa L., Milà-Alomà, Marta, Vrillon, Agathe, Ashton, Nicholas J., Pascoal, Tharick A., Lussier, Firoza, Karikari, Thomas K., Hourregue, Claire, Cognat, Emmanuel, Dumurgier, Julien, Stevenson, Jenna, Rahmouni, Nesrine, Pallen, Vanessa, Poltronetti, Nina M., Salvadó, Gemma, Shekari, Mahnaz, Operto, Gregory, Gispert, Juan Domingo, Minguillon, Carolina, Fauria, Karine, Kollmorgen, Gwendlyn, Suridjan, Ivonne, Zimmer, Eduardo R., Zetterberg, Henrik, Molinuevo, José Luis, Paquet, Claire, Rosa-Neto, Pedro, Blennow, Kaj, Suárez-Calvet, Marc, Beteta, Annabella, Cacciaglia, Raffaele, Cañas, Alba, Deulofeu, Carme, Cumplido, Irene, Dominguez, Ruth, Emilio, Maria, Falcon, Carles, Fuentes, Sherezade, Hernandez, Laura, Huesa, Gema, Huguet, Jordi, Marne, Paula, Menchón, Tania, Operto, Grégory, Polo, Albina, Pradas, Sandra, Soteras, Anna, Vilanova, Marc, Vilor-Tejedor, Natalia, Gaubert, Sinead, Lilamand, Matthieu, Hugon, Jacques, Indart, Sandrine, Fayel, Alexandra, Gmiz, Malika, Francisque, Hélène, Meauzoone, Aurélie, Martinet, Matthieu, Tence, Gabrielle, Chamoun, Mira, Therriault, Joseph, Tissot, Cécile, Bezgin, Gleb, Gauthier, Serge, Gagnon, Guilaine, and Stevensson, Alyssa
- Subjects
medicine.medical_specialty ,macromolecular substances ,Cohort Studies ,Cerebrospinal fluid ,Alzheimer Disease ,Internal medicine ,Glial Fibrillary Acidic Protein ,medicine ,Dementia ,Humans ,Online First ,Demència ,Aged ,Original Investigation ,Aged, 80 and over ,Glial fibrillary acidic protein ,biology ,business.industry ,Research ,Area under the curve ,Plasma sanguini ,Middle Aged ,medicine.disease ,Astrogliosis ,Alzheimer, Malaltia d' ,Endocrinology ,Cross-Sectional Studies ,nervous system ,Concomitant ,Marcadors bioquímics ,biology.protein ,Biomarker (medicine) ,Neurology (clinical) ,Alzheimer's disease ,business ,Biomarkers ,Comments - Abstract
Key Points Question What are the levels of plasma glial fibrillary acidic protein (GFAP) throughout the Alzheimer disease (AD) continuum, and how do they compare with the levels of cerebrospinal fluid (CSF) GFAP? Findings In this cross-sectional study, plasma GFAP levels were elevated in the preclinical and symptomatic stages of AD, with levels higher than those of CSF GFAP. Plasma GFAP had a higher accuracy than CSF GFAP to discriminate between amyloid-β (Aβ)–positive and Aβ-negative individuals, also at the preclinical stage. Meaning This study suggests that plasma GFAP is a sensitive biomarker that significantly outperforms CSF GFAP in indicating Aβ pathology in the early stages of AD., Importance Glial fibrillary acidic protein (GFAP) is a marker of reactive astrogliosis that increases in the cerebrospinal fluid (CSF) and blood of individuals with Alzheimer disease (AD). However, it is not known whether there are differences in blood GFAP levels across the entire AD continuum and whether its performance is similar to that of CSF GFAP. Objective To evaluate plasma GFAP levels throughout the entire AD continuum, from preclinical AD to AD dementia, compared with CSF GFAP. Design, Setting, and Participants This observational, cross-sectional study collected data from July 29, 2014, to January 31, 2020, from 3 centers. The Translational Biomarkers in Aging and Dementia (TRIAD) cohort (Montreal, Canada) included individuals in the entire AD continuum. Results were confirmed in the Alzheimer’s and Families (ALFA+) study (Barcelona, Spain), which included individuals with preclinical AD, and the BioCogBank Paris Lariboisière cohort (Paris, France), which included individuals with symptomatic AD. Main Outcomes and Measures Plasma and CSF GFAP levels measured with a Simoa assay were the main outcome. Other measurements included levels of CSF amyloid-β 42/40 (Aβ42/40), phosphorylated tau181 (p-tau181), neurofilament light (NfL), Chitinase-3-like protein 1 (YKL40), and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and levels of plasma p-tau181 and NfL. Results of amyloid positron emission tomography (PET) were available in TRIAD and ALFA+, and results of tau PET were available in TRIAD. Results A total of 300 TRIAD participants (177 women [59.0%]; mean [SD] age, 64.6 [17.6] years), 384 ALFA+ participants (234 women [60.9%]; mean [SD] age, 61.1 [4.7] years), and 187 BioCogBank Paris Lariboisière participants (116 women [62.0%]; mean [SD] age, 69.9 [9.2] years) were included. Plasma GFAP levels were significantly higher in individuals with preclinical AD in comparison with cognitively unimpaired (CU) Aβ-negative individuals (TRIAD: Aβ-negative mean [SD], 185.1 [93.5] pg/mL, Aβ-positive mean [SD], 285.0 [142.6] pg/mL; ALFA+: Aβ-negative mean [SD], 121.9 [42.4] pg/mL, Aβ-positive mean [SD], 169.9 [78.5] pg/mL). Plasma GFAP levels were also higher among individuals in symptomatic stages of the AD continuum (TRIAD: CU Aβ-positive mean [SD], 285.0 [142.6] pg/mL, mild cognitive impairment [MCI] Aβ-positive mean [SD], 332.5 [153.6] pg/mL; AD mean [SD], 388.1 [152.8] pg/mL vs CU Aβ-negative mean [SD], 185.1 [93.5] pg/mL; Paris: MCI Aβ-positive, mean [SD], 368.6 [158.5] pg/mL; AD dementia, mean [SD], 376.4 [179.6] pg/mL vs CU Aβ-negative mean [SD], 161.2 [67.1] pg/mL). Plasma GFAP magnitude changes were consistently higher than those of CSF GFAP. Plasma GFAP more accurately discriminated Aβ-positive from Aβ-negative individuals than CSF GFAP (area under the curve for plasma GFAP, 0.69-0.86; area under the curve for CSF GFAP, 0.59-0.76). Moreover, plasma GFAP levels were positively associated with tau pathology only among individuals with concomitant Aβ pathology. Conclusions and Relevance This study suggests that plasma GFAP is a sensitive biomarker for detecting and tracking reactive astrogliosis and Aβ pathology even among individuals in the early stages of AD., This cross-sectional cohort study evaluates plasma glial fibrillary acidic protein levels throughout the entire Alzheimer disease continuum, from preclinical Alzheimer disease to Alzheimer disease dementia, compared with cerebrospinal fluid glial fibrillary acidic protein.
- Published
- 2021
7. Validation of the LUMIPULSE automated immunoassay for the measurement of core AD biomarkers in cerebrospinal fluid.
- Author
-
Gobom, Johan, Parnetti, Lucilla, Rosa-Neto, Pedro, Vyhnalek, Martin, Gauthier, Serge, Cataldi, Samuela, Lerch, Ondrej, Laczo, Jan, Cechova, Katerina, Clarin, Marcus, Benet, Andrea L., Pascoal, Tharick A., Rahmouni, Neserine, Vandijck, Manu, Huyck, Else, Le Bastard, Nathalie, Stevenson, Jenna, Chamoun, Mira, Alcolea, Daniel, and Lleó, Alberto
- Subjects
CEREBROSPINAL fluid examination ,CEREBROSPINAL fluid ,IMMUNOASSAY ,TAU proteins ,BIOMARKERS ,PEPTIDES - Abstract
The core cerebrospinal fluid (CSF) biomarkers; total tau (tTau), phospho-tau (pTau), amyloid β 1-42 (Aβ 1-42), and the Aβ 1-42/Aβ 1-40 ratio have transformed Alzheimer's disease (AD) research and are today increasingly used in clinical routine laboratories as diagnostic tools. Fully automated immunoassay instruments with ready-to-use assay kits and calibrators has simplified their analysis and improved reproducibility of measurements. We evaluated the analytical performance of the fully automated immunoassay instrument LUMIPULSE G (Fujirebio) for measurement of the four core AD CSF biomarkers and determined cutpoints for AD diagnosis. Comparison of the LUMIPULSE G assays was performed with the established INNOTEST ELISAs (Fujirebio) for hTau Ag, pTau 181, β-amyloid 1-42, and with V-PLEX Plus Aβ Peptide Panel 1 (6E10) (Meso Scale Discovery) for Aβ 1-42/Aβ 1-40, as well as with a LC-MS reference method for Aβ 1-42. Intra- and inter-laboratory reproducibility was evaluated for all assays. Clinical cutpoints for Aβ 1-42, tTau, and pTau was determined by analysis of three cohorts of clinically diagnosed patients, comprising 651 CSF samples. For the Aβ 1-42/Aβ 1-40 ratio, the cutpoint was determined by mixture model analysis of 2,782 CSF samples. The LUMIPULSE G assays showed strong correlation to all other immunoassays (r>0.93 for all assays). The repeatability (intra-laboratory) CVs ranged between 2.0 and 5.6%, with the highest variation observed for β-amyloid 1-40. The reproducibility (inter-laboratory) CVs ranged between 2.1 and 6.5%, with the highest variation observed for β-amyloid 1-42. The clinical cutpoints for AD were determined to be 409 ng/L for total tau, 50.2 ng/L for pTau 181, 526 ng/L for β-amyloid 1-42, and 0.072 for the Aβ 1-42/Aβ 1-40 ratio. Our results suggest that the LUMIPULSE G assays for the CSF AD biomarkers are fit for purpose in clinical laboratory practice. Further, they corroborate earlier presented reference limits for the biomarkers. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.