Marizzoni, M;
Ferrari, C;
Babiloni, C;
Albani, D;
Barkhof, F;
Cavaliere, L;
Didic, M;
... Frisoni, GB; + view all
(2020)
CSF cutoffs for MCI due to AD depend on APOEε4 carrier status.
Neurobiology of Aging
, 89
pp. 55-62.
10.1016/j.neurobiolaging.2019.12.019.
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Barkhof_Marizzoni - Pharmacog paper on APOE specific CSF cut-offs to identify prodromal AD - NBA_19-118-R1 accepted.pdf - Accepted Version Download (646kB) | Preview |
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.
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