Evaluation of the global association between cholesterol-associated polymorphisms and Alzheimer's disease suggests a role for rs3846662 and HMGCR splicing in disease risk
2011

Cholesterol Genes and Alzheimer's Disease Risk

Sample size: 6000 publication 10 minutes Evidence: moderate

Author Information

Author(s): Christopher R. Simmons, Fanggeng Zou, Steven G. Younkin, Steven Estus

Primary Institution: University of Kentucky and Mayo Clinic College of Medicine

Hypothesis

SNPs associated with plasma cholesterol are also associated with Alzheimer's disease (AD) risk.

Conclusion

Cholesterol-associated SNPs outside of APOE confer a global risk for AD, with specific SNPs linked to both AD risk and age-of-onset.

Supporting Evidence

  • Seventeen non-APOE SNPs were tested for association with AD in ~2,000 AD and ~4,000 non-AD subjects.
  • Rs3846662 and rs1532085 are associated with AD risk and age-of-onset.
  • Rs3846662 affects HMGCR exon 13 splicing, which may influence AD risk.

Takeaway

Some genes related to cholesterol can affect the risk of getting Alzheimer's disease, especially a specific gene variant that might make the disease start earlier.

Methodology

The study evaluated SNPs associated with plasma cholesterol for their association with AD risk using case-control populations across three phases.

Limitations

The study may be limited by the population diversity and the specific SNPs evaluated.

Participant Demographics

The study included approximately 2,000 AD and 4,000 non-AD subjects, primarily Caucasian.

Statistical Information

P-Value

0.004

Confidence Interval

L95: 1.04, U95: 1.21

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1186/1750-1326-6-62

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