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

Camillo Marra, Paolo Maria Rossini, Moira Marizzoni, Clarissa Ferrari, Diego Albani, Frederik Barkhof, Libera Cavaliere, Mira Didic, Gianluigi Forloni, Federica Fusco, Samantha Galluzzi, Tilman Hensch, Jorge Jovicich, José Luis Molinuevo, Flavio Nobili, Lucilla Parnetti, Pierre Payoux, Jean-Philippe Ranjeva, Federica Ribaldi, Elena RolandiAndrea Soricelli, Magda Tsolaki, Pieter Jelle Visser, Jens Wiltfang, Jill C. Richardson, Régis Bordet, Olivier Blin, Giovanni B. Frisoni

Risultato della ricerca: Contributo in rivistaArticolo in rivista

3 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaNeurobiology of Aging
Volume2020
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

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

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