Gender and age modify the association between APOE and AD-related neuropathology.
OBJECTIVE
To assess the impact of apolipoprotein E (APOE) polymorphism on AD-related neurofibrillary tangle (NFT) formation and senile plaques (SP).


METHODS
A sample of 729 routine autopsy brains (359 men, 370 women; age range, 60 to 99 years) was investigated. All brains were classified neuropathologically according to a procedure permitting differentiation of six NFT stages and three SP stages. APOE genotyping was performed on all cases.


RESULTS
The epsilon4 allele of APOE was associated not only with SP (p < 0.0001) but also with NFT formation (p < 0.0001). The effect of the epsilon4 allele on NFT formation was noted at ages > or =80 years (p < 0.0001) but not between ages 60 and 79 years (p = 0.12). An association between the epsilon4 allele and SP for women was found at ages 60 to 79 years (p < 0.0001) but not at > or =80 years of age (p = 0.063). By comparison, men showed an association in both age categories (p = 0.001 and p = 0.001).


CONCLUSIONS
The results confirm the association between the epsilon4 allele and both types of AD-related lesions and show that this association is differentially modified by age and gender.
Ghebremedhin
E
E
Department of Clinical Neuroanatomy, J.W. Goethe-University, Frankfurt, Germany. Ghebremedhin@em.uni-frankfurt.de
Schultz
C
C
Thal
D R
DR
Rüb
U
U
Ohm
T G
TG
Braak
E
E
Braak
H
H
D000367:Age Factors; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012737:Sex Factors
D001057:Apolipoproteins E