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


CONCLUSIONS
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.
Helbecque
Nicole
N
INSERM, U744, Institut Pasteur de Lille, Université de Lille 2, Lille, France.
Codron
Valérie
V
Cottel
Dominique
D
Amouyel
Philippe
P
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D016632:Apolipoprotein A-I / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index; D044465:White People / Q000235:genetics
C505693:APOA1 protein, human; D016632:Apolipoprotein A-I