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Basic Science and Pathogenesis.

Elizabeth J Andrews1, Phong T Ngo1, Jesse R Pascual1

  • 1University of California, Irvine, Irvine, CA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
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Summary
This summary is machine-generated.

Women with Down syndrome and Alzheimer's disease (DSAD) may experience more severe brain pathology, particularly in the occipital cortex. Further research is needed to confirm these sex differences in Alzheimer's disease progression.

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Area of Science:

  • Neurology
  • Genetics
  • Pathology

Background:

  • Biological sex influences Alzheimer's disease (AD) progression, with women exhibiting faster tau accumulation.
  • Individuals with Down syndrome (DS) develop AD neuropathology early, representing a significant genetic cause of AD.
  • Sex-based differences in AD neuropathology within the DS population remain undercharacterized.

Purpose of the Study:

  • To investigate sex differences in AD neuropathology in individuals with Down syndrome.
  • To test the hypothesis that women with DS exhibit more severe AD neuropathology compared to men with DS.
  • To examine p-tau levels in the frontal and occipital cortices as indicators of disease severity.

Main Methods:

  • Postmortem brain tissue from 156 individuals, including DS, DS with AD (DSAD), late-onset AD, and controls, were analyzed.
  • Immunostaining was used to assess levels of phosphorylated tau (p-tau) and amyloid-beta (Aβ) in frontal and occipital cortical regions.
  • Statistical analyses were performed to compare neuropathology loads between sexes and disease groups, adjusting for age.

Main Results:

  • The DSAD group showed significantly higher p-tau and Aβ levels than age-matched controls.
  • p-tau levels were significantly elevated in the DSAD group compared to the late-onset AD group in both cortical regions.
  • While non-significant trends suggested higher p-tau in women with DSAD, p-tau and Aβ were significantly correlated in the occipital cortex of women with DS after age adjustment, but not in men.

Conclusions:

  • Findings suggest women with DSAD may have a more severe pathological burden, particularly in the occipital cortex, compared to men with DSAD.
  • Sex differences in AD pathogenesis may be region-specific and warrant consideration in future research and clinical trial designs.
  • Further studies are necessary to confirm these observed sex differences in Down syndrome-associated Alzheimer's disease.