Alterations in cholesterol metabolism–related genes in sporadic Alzheimer's disease
Open accessAbstract
Genome-wide association studies have identified several cholesterol metabolism-related genes as top risk factors for late-onset Alzheimer's disease (LOAD). We hypothesized that specific genetic variants could act as disease-modifying factors by altering the expression of those genes. Targeted association studies were conducted with available genomic, transcriptomic, proteomic, and histopathological data from 3 independent cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Quebec Founder Population (QFP), and the United Kingdom Brain Expression Consortium (UKBEC). First, a total of 273 polymorphisms located in 17 cholesterol metabolism-related loci were screened for associations with cerebrospinal fluid LOAD biomarkers beta amyloid, phosphorylated tau, and tau (from the ADNI) and with amyloid plaque and tangle densities (from the QFP). Top polymorphisms were then contrasted with gene expression levels measured in 134 autopsied healthy brains (from the UKBEC). In the end, only SREBF2 polymorphism rs2269657 showed significant dual associations with LOAD pathological biomarkers and gene expression levels. Furthermore, SREBF2 expression levels measured in LOAD frontal cortices inversely correlated with age at death; suggesting a possible influence on survival rate.
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Polymorphisms in the SREBF2 gene (rs2269657) have been reported to be associated with the risk of developing late onset AD, and SREBF2 mRNA was reported to be significantly higher in AD temporal cortex and cerebellum.
“Polymorphisms in the SREBF2 gene (rs2269657) have been reported to be associated with the risk of developing late onset AD and SREBF2 mRNA was reported to be significantly higher in AD temporal cortex and cerebellum (55).”
From Regulation of astrocyte lipid metabolism and ApoE secretion by the microglial oxysterol, 25-hydroxycholesterol (2023) · cites this paper as [55]
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- Authors
- Picard, C., Julien, C., Frappier, J., Miron, J., Théroux, L., Dea, D., Breitner, J. C. S., & Poirier, J.
- Affiliations
- Douglas Mental Health University Institute (CA)
- Corresponding author
- Poirier, Judes
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 66
- Pages
- 180.e1-180.e9
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2792472992
- Cited by
- 60
- References
- 7
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 4 · 2023: 8 · 2022: 6 · 2021: 13 · 2020: 5 · 2019: 12 · 2018: 5
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 328 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neurobiology of Aging (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- National Institutes of Health (5u01ag024904-10)
- Canadian Institutes of Health Research
- National Institute on Aging (U01-AG-024904)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- Alzheimer's disease, late-onset Alzheimer's disease, cholesterol metabolism, SREBF2, genetic polymorphism, gene expression, cerebrospinal fluid biomarkers, amyloid-beta, phosphorylated tau, amyloid plaques, neurofibrillary tangles, age at death, frontal cortex
- MeSH terms
- Alzheimer Disease, Cholesterol, Frontal Lobe, Humans, Polymorphism, Genetic, Risk Factors, Cohort Studies, Biomarkers, Gene Expression, Amyloid beta-Peptides, tau Proteins, Sterol Regulatory Element Binding Protein 2, Genome-Wide Association Study, Genetic Loci, Plaque, Amyloid
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