Maternal cognitive decline following a Down syndrome pregnancy

Activity: Talk or presentation › Invited talk

Description

Down syndrome (DS), caused by trisomy 21, leads to life-long overexpression of the human amyloid precursor protein (hAPP) and markedly increases Alzheimer’s disease (AD) risk in affected individuals. However, the impact of DS pregnancies on maternal brain health remains unknown. Here we identify a novel fetomaternal transfer (FMT) pathway in which hAPP+ fetal cells and amyloidogenic hAPP derivatives accumulate and persist in maternal tissues. This transfer induces lasting cognitive impairments accompanied by neuroinflammation, mitochondrial dysfunction, and broad proteomic remodeling. Adoptive transfer of hAPP+ fetal platelets and white blood cells is sufficient to reproduce these deficits, while maternal vaccination targeting hAPP prior to pregnancy prevents them. These findings establish FMT of hAPP as a novel neurodegenerative risk pathway and propose hAPP-specific maternal immunization as a potential protective strategy.
Period1 Dec 2025
Event titleZelman Center Weekly Seminar
Event typeSeminar
LocationBeer sheva, IsraelShow on map
Degree of RecognitionNational

Keywords

  • Down syndrome (DS) (trisomy 21)
  • Alzheimer's disease (AD)
  • Amyloid precursor protein (APP)
  • fetomaternal microchimerism
  • fetal cells
  • fetomaternal transfer (FMT)
  • Neurodegenerative diseases
  • Maternal cognitive decline
  • pregnancy