Distortion of allelic expression of apolipoprotein E in Alzheimer's disease.
The APOE epsilon4 allele is a strong genetic susceptibility factor for Alzheimer's disease. Interaction with other biological factors may modulate the effect of the apoE isoforms. However, previous work suggested that other genetic variability within the APOE locus, influencing the effect of the epsilon4 allele, may exist. Such variability could modify the expression of the APOE gene and, in particular, the level of expression of APOE alleles could be an important determinant of disease pathogenesis. To test this hypothesis we examined the levels of expression of APOE in heterozygotes with AD and in controls, using a new method of semi-quantitation. We report that relative epsilon4 mRNA expression is increased in AD compared with controls and suggest that genetic variability in the neural expression of APOE contributes to disease risk.
Lambert
J C
JC
INSERM Unité 422, Place de Verdun, 59045 Lille Cedex, France.
Pérez-Tur
J
J
Dupire
M J
MJ
Galasko
D
D
Mann
D
D
Amouyel
P
P
Hardy
J
J
Delacourte
A
A
Chartier-Harlin
M C
MC
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D014158:Transcription, Genetic
D053327:Apolipoprotein E4; D001057:Apolipoproteins E