An apolipoprotein A-I gene promoter polymorphism associated with cognitive decline, but not with Alzheimer's disease.

BACKGROUND/AIMS: Accumulating biological and epidemiological evidence suggests a close link between cholesterol metabolism and the pathophysiology of Alzheimer's disease (AD). The observation that the use of statins reduces the risk of AD sustains this hypothesis. Apolipoprotein A-I (APOA1) is the major component of the high-density lipoproteins, particles involved in reverse cholesterol transport. Therefore, genetic polymorphisms in the gene encoding APOA1 might influence cholesterol metabolism and be a risk factor for AD. A previous study suggested an impact of a G-->A polymorphism at position -75 bp in the APOA1 gene on the risk for early-onset AD and on the age at onset of the disease. We studied this polymorphism in 3 independent European population samples.

METHODS

Genotyping was conducted asdescribed in the previous study.

RESULTS

We were unable to show any impact of this polymorphism on the risk of AD. Conversely, subjects bearing the A allele of this polymorphism were at risk of cognitive decline.

CONCLUSION

Our resultssuggest an impact of the G-->A polymorphism at position -75 bp in the APOA1 gene on cognitive impairment, but not on the risk of AD.