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

Ferrari, Clarissa
Babiloni, Claudio
Albani, Diego
Barkhof, Frederik
Cavaliere, Libera
Didic, Mira
Forloni, Gianluigi
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Published in Neurobiology of aging. 2020, vol. 89, p. 55-62
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.
Keywords Alzheimer's diseaseApolipoprotein ECSF cutoffDisease progressionMild cognitive impairment
PMID: 32029236
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Research group Troubles de mémoire et maladie d'Alzeimer (935)
European Commission: PHARMA-COG
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MARIZZONI, Moira et al. CSF cutoffs for MCI due to AD depend on APOEε4 carrier status. In: Neurobiology of Aging, 2020, vol. 89, p. 55-62. doi: 10.1016/j.neurobiolaging.2019.12.019 https://archive-ouverte.unige.ch/unige:140839

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Deposited on : 2020-09-06

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