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.

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.;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
Marizzoni, M.; Ferrari, C.; Babiloni, C.; Albani, D.; Barkhof, F.; Cavaliere, L.; Didic, M.; Forloni, G.; Fusco, F.; Galluzzi, S.; Hensch, T.; Jovicic...espandi
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]
File in questo prodotto:
File Dimensione Formato  
marizzoni_NBA_2019.pdf

Solo gestori archivio

Tipologia: Post-print referato (Refereed author’s manuscript)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 839.9 kB
Formato Adobe PDF
839.9 kB Adobe PDF   Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/282136
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 10
social impact