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

Yu-Ting Hu, Jackson Boonstra, Hugo McGurran, Jochem Stormmesand, Arja Sluiter, Rawien Balesar, Ronald Verwer, Dick Swaab, Ai-Min Bao

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)958-966
JournalNeuropathology and Applied Neurobiology
Volume47
Issue number7
DOIs
Publication statusPublished - 1 Dec 2021
Externally publishedYes

Funding

This study was supported by the Nature Science Foundation of China (91849125,31571048), Programme of Introducing Talents of Discipline to Universities of China (B13026) and the Stichting Vrienden van het Herseninstituut for their support, to Netherlands Brain Bank for providing data and material. Dr Yu‐Ting Hu was supported by the Fund for Cultivation of Innovative Talents, 985 Project of Zhejiang University (188310‐193840101/001). There are no other disclosures.

FundersFunder number
Fund for Cultivation of Innovative Talents, 985 Project of Zhejiang University188310‐193840101/001
Netherlands Brain Bank
Stichting Vrienden van het Herseninstituut
National Natural Science Foundation of China91849125, 31571048
Project 211B13026

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