APOE ε4 lowers age at onset and is a high risk factor for Alzheimer's disease; A case control study from central Norway
Open accessAbstract
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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APOE4 homozygotes have an earlier age of onset for developing Alzheimer's disease (approximately 5 years for each APOE4 allele compared to APOE3 homozygotes).
“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]
The Discussion reports earlier onset of late-onset Alzheimer’s disease with each APOE ε4 allele, but estimates about three years per allele, not five. The Results also report no significant effect on age at onset in early-onset Alzheimer’s disease. (LLM, conf=0.90)
Experimental — accuracy not yet measuredAPOE4 homozygotes have a markedly increased risk of developing Alzheimer's disease (14.5-fold compared to APOE3 homozygotes).
“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]
The Results (Table 3) report a markedly increased odds of AD for APOE ε4/ε4 compared with ε3/ε3, but the odds ratio is 12.9, not 14.5. The Abstract > Results gives the same figure. (LLM, conf=0.90)
Experimental — accuracy not yet measured
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- 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
- Health Sciences › Medicine › Physiology › 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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