The protective gene dose effect of the APOE ε2 allele on gray matter volume in cognitively unimpaired individuals

被引：13

作者：

Salvado, Gemma ^{[1
,2
]}

Ferreira, Daniel ^{[3
,4
]}

Operto, Gregory ^{[1
,2
,5
]}

Cumplido-Mayoral, Irene ^{[1
,6
]}

Arenaza-Urquijo, Eider M. ^{[1
,2
,5
]}

Cacciaglia, Raffaele ^{[1
,2
,5
]}

Falcon, Carles ^{[1
,2
,7
]}

Vilor-Tejedor, Natalia ^{[1
,6
,8
,9
]}

Minguillon, Carolina ^{[1
,2
,5
]}

Groot, Colin ^{[10
]}

van der Flier, Wiesje M. ^{[10
,11
]}

Barkhof, Frederik ^{[12
,13
,14
]}

Scheltens, Philip ^{[10
]}

Ossenkoppele, Rik ^{[10
,15
]}

Kern, Silke ^{[16
]}

Zettergren, Anna ^{[16
]}

Skoog, Ingmar ^{[16
]}

Hort, Jakub ^{[17
,18
,19
]}

Stomrud, Erik ^{[20
,21
]}

van Westen, Danielle ^{[22
,23
]}

Hansson, Oskar ^{[20
,21
]}

Molinuevo, Jose Luis ^{[1
]}

Wahlund, Lars-Olof ^{[3
]}

Westman, Eric ^{[3
,24
]}

Gispert, Juan Domingo ^{[1
,2
,6
,7
]}

机构：

[1] Pasqual Maragall Fdn, Barcelona Beta Brain Res Ctr BBRC, Barcelona, Spain

[2] IMIM Hosp del Mar Med Res Inst, Barcelona, Spain

[3] Karolinska Inst, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Div Clin Geriatr, Stockholm, Sweden

[4] Mayo Clin, Dept Radiol, Rochester, MN USA

[5] CIBER Fragilidad & Envejecimiento Saludable CIBER, Madrid, Spain

[6] Univ Pompeu Fabra, Barcelona, Spain

[7] Ctr Invest Biomed Red Bioingn Biomat & Nanomed CI, Madrid, Spain

[8] Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Barcelona, Spain

[9] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands

[10] Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Amsterdam UMC,Amsterdam Neurosci, Amsterdam, Netherlands

[11] Vrije Univ Amsterdam, Dept Epidemiol & Biostat, Amsterdam UMC, Amsterdam Neurosci, Amsterdam, Netherlands

[12] Vrije Univ Amsterdam Med Ctr, Dept Radiol & Nucl Med, Neurosci Campus Amsterdam, Amsterdam, Netherlands

[13] UCL, Inst Neurol, London, England

[14] UCL, Inst Healthcare Engn, London, England

[15] Lund Univ, Clin Memory Res Unit, Lund, Sweden

[16] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol,Neuropsychiat Epidemiol U, Dept Psychiat & Neurochem,Ctr Ageing & Hlth AgeCa, Gothenburg, Sweden

[17] St Annes Univ Hosp Brno, Int Clin Res Ctr, Brno, Czech Republic

[18] Charles Univ Prague, Fac Med 2, Dept Neurol, Memory Clin, Prague, Czech Republic

[19] Motol Univ Hosp, Prague, Czech Republic

[20] Lund Univ, Dept Clin Sci, Clin Memory Res Unit, Lund, Sweden

[21] Skane Univ Hosp, Memory Clin, Malmo, Sweden

[22] Lund Univ, Inst Clin Sci, Diagnost Radiol, Lund, Sweden

[23] Skane Univ Hosp, Image & Funct, Lund, Sweden

[24] Kings Coll London, Ctr Neuroimaging Sci, Inst Psychiat Psychol & Neurosci, Dept Neuroimaging, London, England

来源：

ALZHEIMERS & DEMENTIA | 2022年 / 18卷 / 07期

基金：

瑞典研究理事会; 加拿大健康研究院; 美国国家卫生研究院;

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; APOLIPOPROTEIN-E; HIPPOCAMPAL VOLUME; ALZHEIMER-DISEASE; MRI; DEMENTIA; YOUNG; NEURODEGENERATION; MECHANISMS; PATHOLOGY; CARRIERS;

D O I：

10.1002/alz.12487

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：1383 / 1395

页数：13

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