Proteomic analysis of APOEε4 carriers implicates lipid metabolism, complement and lymphocyte signaling in cognitive resilience.
Humans
Apolipoprotein E4
/ genetics
Female
Aged
Proteomics
/ methods
Lipid Metabolism
/ physiology
Alzheimer Disease
/ genetics
Cognition
/ physiology
Signal Transduction
/ physiology
Lymphocytes
/ metabolism
Aged, 80 and over
Biomarkers
/ blood
Cognitive Dysfunction
/ genetics
Heterozygote
Male
Cohort Studies
APOE, Resilience
Alzheimer’s disease
Cognition
Immunity
Lipids
Proteomics
Journal
Molecular neurodegeneration
ISSN: 1750-1326
Titre abrégé: Mol Neurodegener
Pays: England
ID NLM: 101266600
Informations de publication
Date de publication:
31 Oct 2024
31 Oct 2024
Historique:
received:
30
03
2024
accepted:
16
10
2024
medline:
1
11
2024
pubmed:
1
11
2024
entrez:
1
11
2024
Statut:
epublish
Résumé
Apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late onset Alzheimer's disease (AD). This case-cohort study used targeted plasma biomarkers and large-scale proteomics to examine the biological mechanisms that allow some APOEε4 carriers to maintain normal cognitive functioning in older adulthood. APOEε4 carriers and APOEε3 homozygotes enrolled in the Women's Health Initiative Memory Study (WHIMS) from 1996 to 1999 were classified as resilient if they remained cognitively unimpaired beyond age 80, and as non-resilient if they developed cognitive impairment before or at age 80. AD pathology (Aß A total of 1610 participants were included (baseline age: 71.3 [3.8 SD] years; all White; 42% APOEε4 carriers). Compared to resilient APOEε4 carriers, non-resilient APOEε4 carriers had lower Aß We identified and replicated a plasma proteomic signature associated with cognitive resilience among APOEε4 carriers. These proteins implicate specific immune processes in the preservation of cognitive status despite elevated genetic risk for AD. Future studies in diverse cohorts will be needed to assess the generalizability of these results.
Sections du résumé
BACKGROUND
BACKGROUND
Apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late onset Alzheimer's disease (AD). This case-cohort study used targeted plasma biomarkers and large-scale proteomics to examine the biological mechanisms that allow some APOEε4 carriers to maintain normal cognitive functioning in older adulthood.
METHODS
METHODS
APOEε4 carriers and APOEε3 homozygotes enrolled in the Women's Health Initiative Memory Study (WHIMS) from 1996 to 1999 were classified as resilient if they remained cognitively unimpaired beyond age 80, and as non-resilient if they developed cognitive impairment before or at age 80. AD pathology (Aß
RESULTS
RESULTS
A total of 1610 participants were included (baseline age: 71.3 [3.8 SD] years; all White; 42% APOEε4 carriers). Compared to resilient APOEε4 carriers, non-resilient APOEε4 carriers had lower Aß
CONCLUSIONS
CONCLUSIONS
We identified and replicated a plasma proteomic signature associated with cognitive resilience among APOEε4 carriers. These proteins implicate specific immune processes in the preservation of cognitive status despite elevated genetic risk for AD. Future studies in diverse cohorts will be needed to assess the generalizability of these results.
Identifiants
pubmed: 39482741
doi: 10.1186/s13024-024-00772-2
pii: 10.1186/s13024-024-00772-2
doi:
Substances chimiques
Apolipoprotein E4
0
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
81Subventions
Organisme : NIA NIH HHS
ID : RF1AG079149
Pays : United States
Organisme : NIA NIH HHS
ID : AG058571
Pays : United States
Organisme : NIA NIH HHS
ID : AG073697
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92021D00001
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92021D00002
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92021D00003
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92021D00004
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92021D00005
Pays : United States
Informations de copyright
© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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