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Gender and age modify the association between APOE and AD-related neuropathology
E Ghebremedhin1, C Schultz, D R Thal
1Department of Clinical Neuroanatomy, J.W. Goethe-University, Frankfurt, Germany. Ghebremedhin@em.uni-frankfurt.de
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).
Conclusion:
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.