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

Dement Geriatr Cogn Disord. 2008;25(2):97-102. doi: 10.1159/000112176. Epub 2007 Dec 10.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / genetics*
  • Apolipoprotein A-I / genetics*
  • Chromosomes, Human, Pair 11 / genetics
  • Cognition Disorders / diagnosis
  • Cognition Disorders / epidemiology
  • Cognition Disorders / genetics*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Polymorphism, Genetic / genetics*
  • Promoter Regions, Genetic / genetics*
  • Risk Factors
  • Severity of Illness Index
  • White People / genetics

Substances

  • APOA1 protein, human
  • Apolipoprotein A-I