Work

Women with Down syndrome show more severe Alzheimer's disease neuropathology with regional differences

Year: 2025

Type: article

Abstract: BACKGROUND: Biological sex affects Alzheimer's disease (AD) progression in the neurotypical population, with women showing more rapid tau accumulation. People with Down syndrome (DS) develop AD neuropathology by the age of 40 years and represent the most common genetic cause of AD. Sex differences in AD neuropathology in Down syndrome (DS) have not been well characterized. We hypothesized that women with DS would show more severe AD neuropathology, indicated by elevated p-tau in the occipital cortex (affected late in disease) relative to frontal cortex (affected earlier in AD), compared to men with DS. METHOD: Postmortem fixed brain tissue from 156 individuals (frontal/occipital regions) were examined by immunostaining serial sections for p-tau (AT8) and Aβ (6E10). Groups were as follows: DS (n = 14/13, age 1-39yr), DS with AD (DSAD) neuropathology (n = 18/19 age 42-61yr), late-onset AD (n = 15/16, age 72-96yr) along with age-matched controls (n = 50/47, age 2-92yr). RESULT: =0.1681). CONCLUSION: Together, these results suggest women with DSAD may have a more severe pathologic burden, specifically in the occipital cortex, an area typically affected later in AD pathogenesis, compared to men with DSAD. Future studies will be required to confirm this difference. Sex differences may also be region-specific, and sex should be considered in design and interpretation of future clinical trials.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz70855_107096