Abstract
Original language | English |
---|---|
Journal | Alzheimer's and Dementia |
Early online date | 2021 |
DOIs | |
Publication status | E-pub ahead of print - 2021 |
Keywords
- Alzheimer's disease
- Alzheimer's disease signature
- apolipoprotein E ε2 carrier
- brain maintenance
- brain morphology
- brain reserve
- cognitive reserve
- magnetic resonance
- multi-site
- resilience signature
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In: Alzheimer's and Dementia, 2021.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - The protective gene dose effect of the APOE ε2 allele on gray matter volume in cognitively unimpaired individuals
AU - Salvadó, Gemma
AU - Ferreira, Daniel
AU - Operto, Grégory
AU - Cumplido-Mayoral, Irene
AU - Arenaza-Urquijo, Eider M.
AU - Cacciaglia, Raffaele
AU - Falcon, Carles
AU - Vilor-Tejedor, Natàlia
AU - Minguillon, Carolina
AU - Groot, Colin
AU - van der Flier, Wiesje M.
AU - Barkhof, Frederik
AU - Scheltens, Philip
AU - Ossenkoppele, Rik
AU - Kern, Silke
AU - Zettergren, Anna
AU - Skoog, Ingmar
AU - Hort, Jakub
AU - Stomrud, Erik
AU - van Westen, Danielle
AU - Hansson, Oskar
AU - Molinuevo, José Luis
AU - Wahlund, Lars-Olof
AU - Westman, Eric
AU - Gispert, Juan Domingo
AU - ALFA study†, BioFINDER, ADNI
AU - Beteta, Annabella
AU - Cañas, Alba
AU - Crous-Bou, Marta
AU - Deulofeu, Carme
AU - Dominguez, Ruth
AU - Emilio, Maria
AU - Fauria, Karine
AU - de Echevarri, José M. González
AU - Grau-Rivera, Oriol
AU - Hernandez, Laura
AU - Huesa, Gema
AU - Huguet, Jordi
AU - Marne, Paula
AU - Menchón, Tania
AU - Milà-Alomà, Marta
AU - Polo, Albina
AU - Pradas, Sandra
AU - Sala-Vila, Aleix
AU - Sánchez-Benavides, Gonzalo
AU - Soteras, Anna
AU - Suárez-Calvet, Marc
AU - Vilanova, Marc
N1 - Funding Information: Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI; National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH‐12‐2‐0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol‐Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann‐La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Funding Information: Data used in pre‐creation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at ( http://adni.loni.usc.edu/wp‐content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf ). The project leading to this study has received funding from “la Caixa” Foundation (ID 100010434), under the agreement LCF/PR/GN17/50300004. Additional support has been received from the Universities and Research Secretariat, Ministry of Business and Knowledge of the Catalan Government under the grant number 2017‐SGR‐892. EMAU is supported by the Spanish Ministry of Science, Innovation and Universities–Spanish State Research Agency (RYC2018‐026053‐I). FB is supported by NIHR biomedical research centre at UCLH. IS is supported by the Swedish Research Council (2019‐02075), Swedish Research Council for Health, Working Life and Wellfare, Swedish state under the agreement between the Swedish government and the county councils, the ALF‐agreement (ALF 716681, ALFGBG‐81392, ALFGBG‐771071), Alzheimerfonden, and Hjärnfonden. DF, LOW, and EW are supported by the Swedish Foundation for Strategic Research (SSF); the Strategic Research Programme in Neuroscience at Karolinska Institutet (StratNeuro); the Swedish Research Council (VR, 2016‐02282); the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet; Center for Innovative Medicine (CIMED); the Swedish Alzheimer Foundation; the Swedish Brain Foundation; the Åke Wiberg Foundation; Demensfonden; Stiftelsen Olle Engkvist Byggmästare; and Birgitta och Sten Westerberg; Funding for Research from Karolinska Institutet; Funding for Geriatric Research from Karolinska Institutet; Stiftelsen Loo och Hans Ostermans; Stiftelsen Gun och Bertil Stohnes; and Stiftelsen Sigurd och Elsa Goljes Minne. JDG is supported by the Spanish Ministry of Economy, and Competitiveness (RYC‐2013‐13054). OH and the BioFINDER study was supported by the Swedish Research Council (2016‐00906), the Knut and Alice Wallenberg foundation (2017‐0383), the Marianne and Marcus Wallenberg foundation (2015.0125), the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University, the Swedish Alzheimer Foundation (AF‐939932), the Swedish Brain Foundation (FO2019‐0326), The Parkinson foundation of Sweden (1280/20), the Skåne University Hospital Foundation (2020‐O000028), Regionalt Forskningsstöd (2020‐0314), and the Swedish federal government under the ALF agreement (2018‐Projekt0279). Publisher Copyright: © 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
PY - 2021
Y1 - 2021
N2 - Introduction: Harboring two copies of the apolipoprotein E (APOE) ε2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described. Methods: Multicenter brain magnetic resonance images (MRIs) from cognitively unimpaired ε2 homozygotes were matched (1:1) against all other APOE genotypes for relevant confounders (n = 223). GM volumes of ε2 genotypic groups were compared to each other and to the reference group (APOE ε3/ε3). Results: Carrying at least one ε2 allele was associated with larger GM volumes in brain areas typically affected by AD and also in areas associated with cognitive resilience. APOE ε2 homozygotes, but not APOE ε2 heterozygotes, showed larger GM volumes in areas related to successful aging. Discussion: In addition to the known resistance against amyloid-β deposition, the larger GM volumes in key brain regions may confer APOE ε2 homozygotes additional protection against AD-related cognitive decline.
AB - Introduction: Harboring two copies of the apolipoprotein E (APOE) ε2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described. Methods: Multicenter brain magnetic resonance images (MRIs) from cognitively unimpaired ε2 homozygotes were matched (1:1) against all other APOE genotypes for relevant confounders (n = 223). GM volumes of ε2 genotypic groups were compared to each other and to the reference group (APOE ε3/ε3). Results: Carrying at least one ε2 allele was associated with larger GM volumes in brain areas typically affected by AD and also in areas associated with cognitive resilience. APOE ε2 homozygotes, but not APOE ε2 heterozygotes, showed larger GM volumes in areas related to successful aging. Discussion: In addition to the known resistance against amyloid-β deposition, the larger GM volumes in key brain regions may confer APOE ε2 homozygotes additional protection against AD-related cognitive decline.
KW - Alzheimer's disease
KW - Alzheimer's disease signature
KW - apolipoprotein E ε2 carrier
KW - brain maintenance
KW - brain morphology
KW - brain reserve
KW - cognitive reserve
KW - magnetic resonance
KW - multi-site
KW - resilience signature
UR - http://www.scopus.com/inward/record.url?scp=85121001961&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/alz.12487
DO - https://doi.org/10.1002/alz.12487
M3 - Article
C2 - 34877786
SN - 1552-5260
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
ER -