CSF cutoffs for MCI due to AD depend on APOEε4 carrier status
- Creators
- Marizzoni M.
- Ferrari C.
- Babiloni C.
- Albani D.
- Barkhof F.
- Cavaliere L.
- Didic M.
- Forloni G.
- Fusco F.
- Galluzzi S.
- Hensch T.
- Jovicich J.
- Marra C.
- Molinuevo J. L.
- Nobili F.
- Parnetti L.
- Payoux P.
- Ranjeva J. -P.
- Ribaldi F.
- Rolandi E.
- Rossini P. M.
- Salvatore M.
- Soricelli A.
- Tsolaki M.
- Visser P. J.
- Wiltfang J.
- Richardson J. C.
- Bordet R.
- Blin O.
- Frisoni G. B.
- Others:
- Marizzoni, M.
- Ferrari, C.
- Babiloni, C.
- Albani, D.
- Barkhof, F.
- Cavaliere, L.
- Didic, M.
- Forloni, G.
- Fusco, F.
- Galluzzi, S.
- Hensch, T.
- Jovicich, J.
- Marra, C.
- Molinuevo, J. L.
- Nobili, F.
- Parnetti, L.
- Payoux, P.
- Ranjeva, J. -P.
- Ribaldi, F.
- Rolandi, E.
- Rossini, P. M.
- Salvatore, M.
- Soricelli, A.
- Tsolaki, M.
- Visser, P. J.
- Wiltfang, J.
- Richardson, J. C.
- Bordet, R.
- Blin, O.
- Frisoni, G. B.
Description
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.
Additional details
- URL
- http://hdl.handle.net/11567/1001997
- URN
- urn:oai:iris.unige.it:11567/1001997
- Origin repository
- UNIGE