TY - JOUR
T1 - CSF cutoffs for MCI due to AD depend on APOEε4 carrier status
AU - Marra, Camillo
AU - Rossini, Paolo Maria
AU - Marizzoni, Moira
AU - Ferrari, Clarissa
AU - Albani, Diego
AU - Barkhof, Frederik
AU - Cavaliere, Libera
AU - Didic, Mira
AU - Forloni, Gianluigi
AU - Fusco, Federica
AU - Galluzzi, Samantha
AU - Hensch, Tilman
AU - Jovicich, Jorge
AU - Molinuevo, José Luis
AU - Nobili, Flavio
AU - Parnetti, Lucilla
AU - Payoux, Pierre
AU - Ranjeva, Jean-Philippe
AU - Ribaldi, Federica
AU - Rolandi, Elena
AU - Soricelli, Andrea
AU - Tsolaki, Magda
AU - Visser, Pieter Jelle
AU - Wiltfang, Jens
AU - Richardson, Jill C.
AU - Bordet, Régis
AU - Blin, Olivier
AU - Frisoni, Giovanni B.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Apolipoprotein E
KW - CSF cutoff
KW - Disease progression
KW - Mild cognitive impairment
KW - Alzheimer's disease
KW - Apolipoprotein E
KW - CSF cutoff
KW - Disease progression
KW - Mild cognitive impairment
UR - http://hdl.handle.net/10807/148740
U2 - 10.1016/j.neurobiolaging.2019.12.019
DO - 10.1016/j.neurobiolaging.2019.12.019
M3 - Article
VL - 2020
SP - N/A-N/A
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
ER -