CSF cutoffs for MCI due to AD depend on APOEε4 carrier status - Institut de Neurosciences des Systèmes
Article Dans Une Revue Neurobiology of Aging Année : 2020

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

1 IRCCS - Centro San Giovanni di Dio, Fatebenefratelli, Brescia
2 UNIROMA - Università degli Studi di Roma "La Sapienza" = Sapienza University [Rome]
3 IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri"
4 Department of Radiology and Nuclear Medicine [Amsterdam]
5 UCL Institute of Neurology, Queen Square [London]
6 INS - Institut de Neurosciences des Systèmes
7 Leipzig University / Universität Leipzig
8 UNITN - Università degli Studi di Trento = University of Trento
9 Unicatt - Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma]
10 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
11 DINOGMI - Dipartimento di Neuroscienze, riabilitazione, oftalmologia, genetica e scienze materno-infantili [Genova]
12 UNIPG - Università degli Studi di Perugia = University of Perugia
13 ToNIC - Toulouse NeuroImaging Center
14 CRMBM - Centre de résonance magnétique biologique et médicale
15 CEMEREM - Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM]
16 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS
17 SDN - Istituto di Ricerca Diagnostica e Nucleare
18 Aristotle University of Thessaloniki
19 Alzheimer Center Amsterdam
20 Universität Duisburg-Essen = University of Duisburg-Essen [Essen]
21 Georg-August-University = Georg-August-Universität Göttingen
22 CIDMA - University of Aveiro
23 GSK - GlaxoSmithKline [Stevenage, UK]
24 LilNCog - Lille Neurosciences & Cognition - U 1172
25 CIC-UPCET - Centre investigation clinique - Unité de pharmacologie clinique et d'évaluations thérapeutiques
26 Laboratory of Neuroimaging of aging, Memory clinic and LANVIE
Mira Didic
Pierre Payoux
Pieter Jelle Visser

Résumé

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.
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Dates et versions

hal-03500710 , version 1 (14-09-2024)

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Moira Marizzoni, Clarissa Ferrari, Claudio Babiloni, Diego Albani, Frederik Barkhof, et al.. CSF cutoffs for MCI due to AD depend on APOEε4 carrier status. Neurobiology of Aging, 2020, 89, pp.55-62. ⟨10.1016/j.neurobiolaging.2019.12.019⟩. ⟨hal-03500710⟩
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