Gender differences in Alzheimer's disease neuropathology
E.H. Corder, E. Ghebremedhin, D.R. Thal, T.G. Ohm, H. Braak
Duke University, Center for Demographic Studies, 2117 Campus Drive, Box 90408, Durham, NC 27708-0408, U.S.A.
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.
Key words:
dementia; gender differences; neurodegeneration; Alzheimer disease
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