E.H. Corder, E. Ghebremedhin, D.R. Thal, T.G. Ohm, H. Braak

Women are thought to have a higher risk of developing Alzheimer's disease (AD) compared to men, partly because they live longer. We investigated whether women have an accelerated pathogenesis of AD which would account for higher age-specific disease occurrence. A total of 3165 men and 2450 women were investigated. Braak stages for neurofibrillary tangles (NFT) (I-VI, recoded 1 to 6 for analysis) and senile plaque (SP) (A-C, recoded 1 to 3) were compared for men and women for each decade of age from 20-29 years onward. Men and women were equally likely to have AD changes at each age. Women were more likely to have more brain regions containing lesions once the process had been initiated. The gender-gaps were largest at age 65 (SP: mean 0.8 vs 0.6 (p=0.001); NFT: mean 1.4 vs 1.2 (p=0.01)). From age 50 to 90 women had the same mean NFT stage as found for men three years older. There was a biphasic relationship between the staging systems in that SP stage C was found at NFT stages 4 to 6, i.e. IV to VI. At younger ages little SP was associated with NFT stages 1-3, i.e. I to III. With increasing age SP distribution at early NFT stages increased, most evidently for women from age 55 to 65. At age 95 many women had SP stage C even at NFT stage 3, i.e. III. The increase in SP stage at early NFT stages was more gradual for men. Each gender difference was largely attributable to women who carried the type 4 allele for the apolipoprotein E gene. We conclude that a gender-gap in Alzheimer neuropathogenesis is present from earliest stages and is APOE4-related, and that men and women may differ in the pathologic substrate for Alzheimer dementia.

Keywords (Optional): 
gender differences
Alzheimer disease