Genetic characterization of the ALFA study: Uncovering genetic profiles in the Alzheimer's continuum

Natalia Vilor-Tejedor*, Patricia Genius, Blanca Rodríguez-Fernández, Carolina Minguillón, Iman Sadeghi, Armand González-Escalante, Marta Crous-Bou, Marc Suárez-Calvet, Oriol Grau-Rivera, Anna Brugulat-Serrat, Gonzalo Sánchez-Benavides, Manel Esteller, Karine Fauria, José Luis Molinuevo, Arcadi Navarro, Juan Domingo Gispert*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

INTRODUCTION:

In 2013, the ALzheimer's and FAmilies (ALFA) project was established to investigate pathophysiological changes in preclinical Alzheimer's disease (AD), and to foster research on early detection and preventive interventions. 

METHODS: 

We conducted a comprehensive genetic characterization of ALFA participants with respect to neurodegenerative/cerebrovascular diseases, AD biomarkers, brain endophenotypes, risk factors and aging biomarkers. We placed particular emphasis on amyloid/tau status and assessed gender differences. Multiple polygenic risk scores were computed to capture different aspects of genetic predisposition. We additionally compared AD risk in ALFA to that across the full disease spectrum from the Alzheimer's Disease Neuroimaging Initiative (ADNI). 

RESULTS: 

Results show that the ALFA project has been successful at establishing a cohort of cognitively unimpaired individuals at high genetic predisposition of AD. 

DISCUSSION: 

It is, therefore, well-suited to study early pathophysiological changes in the preclinical AD continuum. Highlights Prevalence of ε4 carriers in ALzheimer and FAmilies (ALFA) is higher than in the general European population The ALFA study is highly enriched in Alzheimer's disease (AD) genetic risk factors beyond APOE AD genetic profiles in ALFA are similar to clinical groups along the continuum ALFA has succeeded in establishing a cohort of cognitively unimpaired individuals at high genetic AD risk ALFA is well suited to study pathogenic events/early pathophysiological changes in AD.

Original languageEnglish
Pages (from-to)1703-1715
Number of pages13
JournalAlzheimer's and Dementia
Volume20
Issue number3
Early online date13 Dec 2023
DOIs
Publication statusPublished - Mar 2024

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

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