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APOE ε4 lowers age at onset and is a high risk factor for Alzheimer's disease; A case control study from central Norway
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BACKGROUND: The objective of this study was to analyze factors influencing the risk and timing of Alzheimer's disease (AD) in central Norway. The APOE epsilon4 allele is the only consistently identified risk factor for late onset Alzheimer's disease (LOAD). We have described the allele frequencies of the apolipoprotein E gene (APOE) in a large population of patients with AD compared to the frequencies in a cognitively-normal control group, and estimated the effect of the APOE epsilon4 allele on the risk and the age at onset of AD in this population. METHODS: 376 patients diagnosed with AD and 561 cognitively-normal control individuals with no known first degree relatives with dementia were genotyped for the APOE alleles. Allele frequencies and genotypes in patients and control individuals were compared. Odds Ratio for developing AD in different genotypes was calculated. RESULTS: Odds Ratio (OR) for developing AD was significantly increased in carriers of the APOE epsilon4 allele compared to individuals with the APOE epsilon3/epsilon3 genotype. Individuals carrying APOE epsilon4/epsilon4 had OR of 12.9 for developing AD, while carriers of APOE epsilon2/epsilon4 and APOE epsilon3/epsilon4 had OR of 3.2 and 4.2 respectively. The effect of the APOE epsilon4 allele was weaker with increasing age. Carrying the APOE epsilon2 allele showed no significant protective effect against AD and did not influence age at onset of the disease. Onset in LOAD patients was significantly reduced in a dose dependent manner from 78.4 years in patients without the APOE epsilon4 allele, to 75.3 in carriers of one APOE epsilon4 allele and 72.9 in carriers of two APOE epsilon4 alleles. Age at onset in early onset AD (EOAD) was not influenced by APOE epsilon4 alleles. CONCLUSION: APOE epsilon4 is a very strong risk factor for AD in the population of central Norway, and lowers age at onset of LOAD significantly.
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“as well as an earlier age of onset for developing the disease (approximately 5 years for each APOE4 allele compared to APOE3 homozygotes).6,9,10”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [10]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“APOE4 homozygotes have a markedly increased risk of developing AD (14.5-fold compared to APOE3 homozygotes)”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [10]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Each ApoE4 allele reduces the age of Alzheimer’s disease (AD) onset by approximately 3–5 years compared to ApoE3 homozygotes, which comprise ~80% of the human population (Roses, 1994; Sando et al., 2008).”
From NHE6 depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load (2021) · cites this paper as Sando et al., 2008
Experimental — accuracy not yet measuredIn the citing paper
“Each ApoE4 allele reduces the age of Alzheimer’s disease (AD) onset by approximately 3–5 years compared to ApoE3 homozygotes, which comprise ~80% of the human population (Roses, 1994; Sando et al., 2008).”
From NHE6 depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load (2021) · cites this paper as Sando et al., 2008
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Metadata
- Authors
- Sando, S. B., Melquist, S., Cannon, A., Hutton, M. L., Sletvold, O., Saltvedt, I., White, L. R., Lydersen, S., & Aasly, J. O.
- Affiliations
- Norwegian University of Science and Technology (NO)
- Mayo Clinic (US)
- Corresponding author
- Sando, Sigrid B
- Venue
- BMC Neurology
- Published
- 2008-04-16
- Volume
- 8
- Issue
- 1
- Pages
- 9-9
- ISSN
- 1471-2377 (ISSN-L)
- PMC
- PMC2375917
- OpenAlex
- W1972488785
- Cited by
- 261
- References
- 39
- Citations by year
- 2026: 11 · 2025: 24 · 2024: 21 · 2023: 12 · 2022: 22 · 2021: 20 · 2020: 13 · 2019: 12 · 2018: 17 · 2017: 15 · 2016: 13 · 2015: 16 · 2014: 10 · 2013: 10 · 2012: 11
- FWCI
- 7.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Neurology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- BIBSYS Brage (BIBSYS (Norway)) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Funders
- Mayo Foundation for Medical Education and Research (AG17216)
- Norges Forskningsråd (153487/V50)
- National Institutes of Health (AG17216)
- National Institute on Aging (P01-AG-17216, F32AG024030, AG 24030, P01AG017216)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- Alzheimer's disease, APOE ε4, apolipoprotein E, late-onset Alzheimer's disease, age of onset, genetic risk factors, APOE ε2 allele, allele frequency, early-onset Alzheimer's disease, dose-dependent effects
- MeSH terms
- Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Female, Gene Frequency, Humans, Male, Norway, Risk Factors, Odds Ratio, Case-Control Studies, Age of Onset, Apolipoprotein E4
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