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

Aged Aged, 80 and over Alzheimer Disease / complications Amyloid beta-Peptides / cerebrospinal fluid Apolipoproteins E / genetics Biomarkers / cerebrospinal fluid Cognitive Dysfunction / diagnosis Cohort Studies Female Heterozygote Humans Male Peptide Fragments / cerebrospinal fluid tau Proteins / cerebrospinal fluid

Alzheimer's disease Apolipoprotein E CSF cutoff Disease progression Mild cognitive impairment

Journal

Neurobiology of aging

ISSN: 1558-1497

Titre abrégé: Neurobiol Aging

Pays: United States

ID NLM: 8100437

Informations de publication

Date de publication:
05 2020

Historique:

received: 19 02 2019

revised: 20 12 2019

accepted: 21 12 2019

pubmed: 8 2 2020

medline: 24 9 2020

entrez: 8 2 2020

Statut: ppublish

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.

Identifiants

DOI: 10.1016/j.neurobiolaging.2019.12.019 PMID: 32029236

pubmed: 32029236

pii: S0197-4580(19)30448-8

doi: 10.1016/j.neurobiolaging.2019.12.019

pii:

doi:

Substances chimiques

Amyloid beta-Peptides 0

Apolipoproteins E 0

Biomarkers 0

Peptide Fragments 0

amyloid beta-protein (1-42) 0

tau Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

55-62

Subventions

Organisme : Department of Health

Pays : United Kingdom