Wednesday, 27.05.2026, Day 1
Time: 09:20 – 10:15
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Microchimerism during Down Syndrome pregnancies causes maternal cognitive decline
Prof. Eitan Okun
Head, the Paul Feder laboratory for Alzheimer’s disease research
The Mina and Everard Goodman Faculty of Life Sciences
Bar Ilan University, Ramat-Gan, Israel
https://sites.biu.ac.il/en/okun-lab
Down Syndrome (DS), caused by trisomy of chromosome 21, is the most common genetic form of intellectual disability, affecting 1 in 750-1000 live births worldwide. Individuals with DS face an increased risk of Alzheimer’s disease (AD) due to the life-long over-expression of the amyloid precursor protein (APP) gene encoded on chromosome 21. Pregnancies involving a DS-affected fetus increase the mother’s risk of late-onset AD (LOAD) almost five-fold compared to pregnancies with a fetus with other intellectual disabilities through mechanisms that remain unknown. We report that fetomaternal transfer of human APP (hAPP) impairs maternal cognitive function dose-dependently in a mechanism that involved microchimerism. Maternal vaccination targeting APP before pregnancy mitigated short-term memory loss. Our findings provide mechanistic insights into the increased LOAD risk in mothers of DS individuals and suggest possible preventive measures.
The intersection of maternal microchimerism and infectious disease
Whitney Harrington
Seattle Children’s Hospital, USA
Mothers transmit cells to their offspring in utero and likely via postnatal breastmilk exposure. The transmission of these cells is impacted by maternal immune stimuli in pregnancy including placental malaria, peripheral malaria, HIV, and potentially vaccination. Prior work has demonstrated that these cells are enriched for memory T cell populations, and we hypothesize that they may directly and indirectly impact fetal and postnatal immunity in the offspring. For example, we have found that maternal microchimerism at birth is associated with augmented response to Bacillus Calmette–Guérin (BCG) vaccination and reduced susceptibility to symptomatic malaria, respiratory infection, and non-malaria fever. To better understand the mechanism of this protection, we have recently developed an approach to isolate rare maternal T cells from the offspring and investigate their transcriptional profile. Using this approach and others, we have identified Falciparum malaria-, cytomegalovirus- (CMV), and mycobacterium-specific T cells in select offspring, representing the direct transmission of cellular pathogen-specific immunity. In addition, we have recently developed an approach to massively expand maternal microchimeric T cells to better enable functional screening for potential antigen specificity. Further, we have identified an associated between the presence of maternal cells at birth and altered prenatal immune priming against malaria, suggesting that maternal microchimerism may also indirectly impact fetal immunity. These data suggest that maternal microchimerism plays an important and underappreciated role in providing “active” protection to the offspring against infection.