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

Salvadó, Gemma LU ; Ferreira, Daniel ; Operto, Grégory ; Cumplido-Mayoral, Irene ; Arenaza-Urquijo, Eider M. ; Cacciaglia, Raffaele ; Falcon, Carles ; Vilor-Tejedor, Natàlia ; Minguillon, Carolina and Groot, Colin LU , et al. (2022) In Alzheimer's and Dementia 18(7). p.1383-1395
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
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
in
Alzheimer's and Dementia
volume
18
issue
7
pages
1383 - 1395
publisher
Wiley
external identifiers
  • pmid:34877786
  • scopus:85121001961
ISSN
1552-5260
DOI
10.1002/alz.12487
language
English
LU publication?
yes
id
79849a2d-00f8-489c-902c-41570f65af6b
date added to LUP
2022-02-01 17:04:53
date last changed
2024-04-20 20:13:45
@article{79849a2d-00f8-489c-902c-41570f65af6b,
  abstract     = {{<p>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.</p>}},
  author       = {{Salvadó, Gemma and Ferreira, Daniel and Operto, Grégory and Cumplido-Mayoral, Irene and Arenaza-Urquijo, Eider M. and Cacciaglia, Raffaele and Falcon, Carles and Vilor-Tejedor, Natàlia and Minguillon, Carolina and Groot, Colin and van der Flier, Wiesje M. and Barkhof, Frederik and Scheltens, Philip and Ossenkoppele, Rik and Kern, Silke and Zettergren, Anna and Skoog, Ingmar and Hort, Jakub and Stomrud, Erik and van Westen, Danielle and Hansson, Oskar and Molinuevo, José Luis and Wahlund, Lars Olof and Westman, Eric and Gispert, Juan Domingo}},
  issn         = {{1552-5260}},
  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}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{1383--1395}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{The protective gene dose effect of the APOE ε2 allele on gray matter volume in cognitively unimpaired individuals}},
  url          = {{http://dx.doi.org/10.1002/alz.12487}},
  doi          = {{10.1002/alz.12487}},
  volume       = {{18}},
  year         = {{2022}},
}