Sex differences in the neuropathological hallmarks of Alzheimer’s disease: focus on cognitively intact elderly individuals

AIMS: Women are more vulnerable to Alzheimer's disease (AD) than men. We investigated (i) whether and at what age the AD hallmarks, that is, β‐amyloid (Aβ) and hyperphosphorylated Tau (p‐Tau) show sex differences; and (ii) whether such sex differences may occur in cognitively intact elderly individuals. METHODS: We first analysed the entire post‐mortem brain collection of all non‐demented ‘controls’ and AD donors from our Brain Bank (245 men and 403 women), for the presence of sex differences in AD hallmarks. Second, we quantitatively studied possible sex differences in Aβ, Aβ42 and p‐Tau in the entorhinal cortex of well‐matched female (n = 31) and male (n = 21) clinically cognitively intact elderly individuals. RESULTS: Women had significantly higher Braak stages for tangles and amyloid scores than men, after 80 years. In the cognitively intact elderly, women showed higher levels of p‐Tau, but not Aβ or Aβ42, in the entorhinal cortex than men, and a significant interaction of sex with age was found only for p‐Tau but not Aβ or Aβ42. CONCLUSIONS: Enhanced p‐Tau in the entorhinal cortex may play a major role in the vulnerability to AD in women.