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. © 2020 Elsevier Inc. All rights reserved.
CSF cutoffs for MCI due to AD depend on APOEε4 carrier status / 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.. - In: NEUROBIOLOGY OF AGING. - ISSN 0197-4580. - 89:(2020), pp. 55-62. [10.1016/j.neurobiolaging.2019.12.019]
CSF cutoffs for MCI due to AD depend on APOEε4 carrier status
Ferrari C.Secondo
;Fusco F.;Jovicich J.;
2020-01-01
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. © 2020 Elsevier Inc. All rights reserved.| File | Dimensione | Formato | |
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