Acta Neuropathologica

, Volume 136, Issue 6, pp 887–900 | Cite as

Sex differences in Alzheimer’s disease and common neuropathologies of aging

  • Shahram OveisgharanEmail author
  • Zoe Arvanitakis
  • Lei Yu
  • Jose Farfel
  • Julie A. Schneider
  • David A. Bennett
Original Paper


Alzheimer’s dementia is significantly more common in women than in men. However, few pathological studies have addressed sex difference in Alzheimer’s disease (AD) and other brain pathologies. We leveraged postmortem data from 1453 persons who participated in one of two longitudinal community-based studies of older adults, the Religious Orders Study and the Rush Memory and Aging Project. Postmortem examination identified AD pathologies, neocortical Lewy bodies, DNA-binding protein 43 (TDP-43), hippocampal sclerosis, gross and micro infarcts, atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy. Linear and logistic regressions examined the association of sex with each of the pathologic measures. Two-thirds of subjects were women (n = 971; 67%), with a mean age at death of 89.8 (SD = 6.6) years in women and 87.3 (SD = 6.6) in men. Adjusted for age and education, women had higher levels on a global measure of AD pathology (estimate = 0.102, SE = 0.022, p < 0.001), and tau tangle density in particular (estimate = 0.334, SE = 0.074, p < 0.001), and there was a borderline difference between women and men in amyloid-β load (estimate = 0.124, SE = 0.065, p = 0.056). In addition, compared to men, women were more likely to have more severe arteriolosclerosis (OR = 1.28, 95% CI:1.04–1.58, p = 0.018), and less likely to have gross infarcts (OR = 0.78, 95% CI:0.61–0.98, p = 0.037), although the association with gross infarct was attenuated after controlling for vascular risk factors. These data help elucidate the neuropathologic footprint of sex difference in AD and other common brain pathologies of aging.


Alzheimer disease Sex Pathology Tau proteins Amyloid Arteriolosclerosis 



We thank the participants in the ROS and MAP. We also thank the staff and faculty of the Rush Alzheimer’s Disease Center. This work was supported by the National Institute of Health grants R01AG17917, P30AG10161, R01AG15819, and RO1NS084965.

Supplementary material

401_2018_1920_MOESM1_ESM.docx (49 kb)
Supplementary material 1 (DOCX 49 kb)


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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Rush Alzheimer’s Disease CenterRush University Medical CenterChicagoUSA
  2. 2.Department of Neurological SciencesRush University Medical CenterChicagoUSA
  3. 3.Department of PathologyRush University Medical CenterChicagoUSA
  4. 4.Department of GeriatricsUniversity of Sao Paulo Medical SchoolSao PauloBrazil

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