Genetic characterization of the ALFA study : Uncovering genetic profiles in the Alzheimer's continuum
Vilor-Tejedor, Natalia (Institut Hospital del Mar d'Investigacions Mèdiques)
Genius, Patricia (Institut Hospital del Mar d'Investigacions Mèdiques)
Rodríguez-Fernández, Blanca (Institut Hospital del Mar d'Investigacions Mèdiques)
Minguillón, Carolina (Institut Hospital del Mar d'Investigacions Mèdiques)
Sadeghi, Iman (Centre de Regulació Genòmica)
González-Escalante, Armand (Institut Hospital del Mar d'Investigacions Mèdiques)
Crous-Bou, Marta (Hospital Universitari de Bellvitge)
Suárez-Calvet, Marc (Institut Hospital del Mar d'Investigacions Mèdiques)
Grau-Rivera, Oriol (Institut Hospital del Mar d'Investigacions Mèdiques)
Brugulat-Serrat, Anna (Institut Hospital del Mar d'Investigacions Mèdiques)
Sánchez-Benavides, Gonzalo (Institut Hospital del Mar d'Investigacions Mèdiques)
Esteller, M (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Fauria, Karine (Pasqual Maragall Foundation)
Molinuevo, José Luis (Pasqual Maragall Foundation)
Navarro, Arcadi 1969- (Universitat Pompeu Fabra)
Gispert, Juan Domingo (Institut Hospital del Mar d'Investigacions Mèdiques)

Date:	2023
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.
Grants:	European Commission. Horizon 2020 847648
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	AD continuum ; ALFA study ; Alzheimer's disease ; Neurogenetics ; Neurological diseases ; Prevention
Published in:	Alzheimer's & Dementia, 2023 , ISSN 1552-5279

DOI: 10.1002/alz.13537
PMID: 38088508

13 p, 1.9 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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Articles > Published articles