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

doi:10.1002/alz.13537

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

Clinical Genetics

Pasqual Maragall Foundation
Centre for Genomic Regulation
Hospital del Mar
Centro de Investigación Biomédica en Red (CIBER)
Pompeu Fabra University
Harvard T.H. Chan School of Public Health
Hospital Durán i Reynals
Global Brain Health Institute
Josep Carreras Leukaemia Research Institute
ICREA
University of Barcelona
H. Lundbeck A/S
Institute of Evolutionary Biology (CSIC-UPF)
Centro Nacional de Investigaciones Cardiovasculares
the Barcelonaβeta Brain Research Center
CRG, Inc.
Hospital del Mar Medical Research Institute (IMIM)

Research output: Contribution to journal › Article › Academic › peer-review

13 Citations (Scopus)

32 Downloads (Pure)

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 language	English
Pages (from-to)	1703-1715
Number of pages	13
Journal	Alzheimer's and Dementia
Volume	20
Issue number	3
Early online date	13 Dec 2023
DOIs	https://doi.org/10.1002/alz.13537
Publication status	Published - Mar 2024

Bibliographical note

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Cite this

Vilor-Tejedor, N., Genius, P., Rodríguez-Fernández, B., Minguillón, C., Sadeghi, I., González-Escalante, A., Crous-Bou, M., Suárez-Calvet, M., Grau-Rivera, O., Brugulat-Serrat, A., Sánchez-Benavides, G., Esteller, M., Fauria, K., Molinuevo, J. L., Navarro, A., & Gispert, J. D. (2024). Genetic characterization of the ALFA study: Uncovering genetic profiles in the Alzheimer's continuum. Alzheimer's and Dementia, 20(3), 1703-1715. https://doi.org/10.1002/alz.13537

@article{03f1879878f341f18f5645109a98db58,

title = "Genetic characterization of the ALFA study: Uncovering genetic profiles in the Alzheimer's continuum",

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.",

author = "Natalia Vilor-Tejedor and Patricia Genius and Blanca Rodr{\'i}guez-Fern{\'a}ndez and Carolina Minguill{\'o}n and Iman Sadeghi and Armand Gonz{\'a}lez-Escalante and Marta Crous-Bou and Marc Su{\'a}rez-Calvet and Oriol Grau-Rivera and Anna Brugulat-Serrat and Gonzalo S{\'a}nchez-Benavides and Manel Esteller and Karine Fauria and Molinuevo, \{Jos{\'e} Luis\} and Arcadi Navarro and Gispert, \{Juan Domingo\}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2024",

month = mar,

doi = "10.1002/alz.13537",

language = "English",

volume = "20",

pages = "1703--1715",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

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}

Vilor-Tejedor, N, Genius, P, Rodríguez-Fernández, B, Minguillón, C, Sadeghi, I, González-Escalante, A, Crous-Bou, M, Suárez-Calvet, M, Grau-Rivera, O, Brugulat-Serrat, A, Sánchez-Benavides, G, Esteller, M, Fauria, K, Molinuevo, JL, Navarro, A & Gispert, JD 2024, 'Genetic characterization of the ALFA study: Uncovering genetic profiles in the Alzheimer's continuum', Alzheimer's and Dementia, vol. 20, no. 3, pp. 1703-1715. https://doi.org/10.1002/alz.13537

TY - JOUR

T1 - Genetic characterization of the ALFA study

T2 - Uncovering genetic profiles in the Alzheimer's continuum

AU - Vilor-Tejedor, Natalia

AU - Genius, Patricia

AU - Rodríguez-Fernández, Blanca

AU - Minguillón, Carolina

AU - Sadeghi, Iman

AU - González-Escalante, Armand

AU - Crous-Bou, Marta

AU - Suárez-Calvet, Marc

AU - Grau-Rivera, Oriol

AU - Brugulat-Serrat, Anna

AU - Sánchez-Benavides, Gonzalo

AU - Esteller, Manel

AU - Fauria, Karine

AU - Molinuevo, José Luis

AU - Navarro, Arcadi

AU - Gispert, Juan Domingo

PY - 2024/3

Y1 - 2024/3

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85179372515

U2 - 10.1002/alz.13537

DO - 10.1002/alz.13537

M3 - Article

C2 - 38088508

AN - SCOPUS:85179372515

SN - 1552-5260

VL - 20

SP - 1703

EP - 1715

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 3

ER -

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

Abstract

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