期刊
ALZHEIMERS & DEMENTIA
卷 18, 期 7, 页码 1383-1395出版社
WILEY
DOI: 10.1002/alz.12487
关键词
Alzheimer's disease; Alzheimer's disease signature; apolipoprotein E epsilon 2 carrier; brain maintenance; brain morphology; brain reserve; cognitive reserve; magnetic resonance; multi-site; resilience signature
资金
- Alzheimer's Disease Neuroimaging Initiative (ADNI
- National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen
- BristolMyers Squibb Company
- CereSpir, Inc.
- Cogstate
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd.
- 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
- Transition Therapeutics
- Canadian Institutes of Health Research
- la Caixa Foundation [100010434, LCF/PR/GN17/50300004]
- Universities and Research Secretariat, Ministry of Business and Knowledge of the Catalan Government [2017-SGR-892]
- Spanish Ministry of Science, Innovation and Universities-Spanish State Research Agency [RYC2018-026053-I]
- NIHR biomedical research centre at UCLH
- Swedish Research Council [2019-02075, 2016-02282, 2016-00906]
- Swedish state government
- Swedish county councils, the ALF-agreement [ALF 716681, ALFGBG-81392, ALFGBG-771071]
- Alzheimerfonden
- Hjarnfonden
- Swedish Foundation for Strategic Research (SSF)
- Strategic Research Programme in Neuroscience at Karolinska Institutet (StratNeuro)
- Stockholm County Council
- Karolinska Institutet
- Center for Innovative Medicine (CIMED)
- Swedish Alzheimer Foundation
- Swedish Brain Foundation
- Ake Wiberg Foundation
- Demensfonden
- Stiftelsen Olle Engkvist Byggmastare
- Birgitta och Sten Westerberg
- Stiftelsen Loo och Hans Ostermans
- Stiftelsen Gun och Bertil Stohnes
- Stiftelsen Sigurd och Elsa Goljes Minne
- Spanish Ministry of Economy, and Competitiveness [RYC-2013-13054]
- Knut and Alice Wallenberg foundation [2017-0383]
- Marianne and Marcus Wallenberg foundation [2015.0125]
- Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University
- Swedish Alzheimer Foundation [AF939932]
- Swedish Brain Foundation [FO2019-0326]
- Parkinson foundation of Sweden [1280/20]
- Skane University Hospital Foundation [2020-O000028]
- Regionalt Forskningsstod [2020-0314]
- Swedish federal government under the ALF agreement [2018Projekt0279]
- Vinnova [2016-02282] Funding Source: Vinnova
- Swedish Research Council [2016-02282, 2019-02075] Funding Source: Swedish Research Council
Carrying the APOE ε2 allele is associated with larger gray matter volumes in brain regions affected by AD, providing additional protection against cognitive decline. Homozygotes for the ε2 allele exhibit larger GM volumes in regions related to successful aging.
Introduction: Harboring two copies of the apolipoprotein E (APOE) epsilon 2 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 epsilon 2 homozygotes were matched (1:1) against all other APOE genotypes for relevant confounders (n = 223). GM volumes of epsilon 2 genotypic groups were compared to each other and to the reference group (APOE epsilon 3/epsilon 3). Results: Carrying at least one epsilon 2 allele was associated with larger GM volumes in brain areas typically affected by AD and also in areas associated with cognitive resilience. APOE epsilon 2 homozygotes, but not APOE epsilon 2 heterozygotes, showed larger GM volumes in areas related to successful aging. Discussion: In addition to the known resistance against amyloid-beta deposition, the larger GM volumes in key brain regions may confer APOE epsilon 2 homozygotes additional protection against AD-related cognitive decline.
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