APOE and dementia - resequencing and genotyping in 105,597 individuals.
Level 3 - non-randomized controlled study
Non-randomized genetic association cohort study.
PubMed 32808727 · doi:10.1002/alz.12165
What was done
The APOE gene was sequenced in 10,369 individuals, and nine amino acid-changing variants (frequencies ≥2/10,000) were subsequently genotyped in 95,228 individuals (total n = 105,597). Plasma apoE levels were measured directly. Authors evaluated the risk of all-cause dementia and Alzheimer's disease (AD) according to genetically determined apoE levels, adjusting for APOE ɛ2/ɛ3/ɛ4 genotype status.
What was found
Risk of all-cause dementia and AD increased with decreasing genetically determined apoE levels (P = 5 × 10⁻⁴ for all dementia and P = 1 × 10⁻⁴ for AD after adjusting for APOE ɛ2/ɛ3/ɛ4). Compared with the ɛ33 genotype group, hazard ratios (95% CI) for the group with the genetically lowest apoE were 2.76 (1.39 to 5.47) for all dementia and 4.92 (2.36 to 10.29) for AD. Genetically high apoE levels were associated with decreased risk.
Why it matters
This indicates that dementia risk relates directly to genetic variants altering overall apoE expression levels, not just the canonical ɛ2/ɛ3/ɛ4 isoform structure.
Limits
The abstract does not specify cohort demographics, ancestry, follow-up duration, or diagnostic criteria for dementia and AD. It measures peripheral plasma apoE rather than central nervous system apoE concentrations.
Cited by
- context Serum levels of APOE are more predictive of Alzheimer's disease risk than APOE genotype.