Environmental enrichment reverses Aβ pathology during pregnancy in a mouse model of Alzheimer’s disease

Stephanie Ziegler-Waldkirch, Karin Marksteiner, Johannes Stoll, Paolo d´Errico, Marina Friesen, Denise Eiler, Lea Neudel, Verena Sturn, Isabel Opper, Moumita Datta, Marco Prinz, Melanie Meyer-Luehmann

Several studies suggest that women have a higher risk to develop Alzheimer's disease (AD) than men. In particular, the number of pregnancies was shown to be a risk factor for AD and women with several pregnancies on average had an earlier onset of the disease, thus making childbearing a risk factor. However, the impact of being pregnant on Aβ plaque pathology and adult neurogenesis still remains elusive. Postmortem analysis revealed that pregnant 5xFAD transgenic mice had significantly more Aβ plaques in the hippocampus from G10 onwards and that the number of Ki67 and DCX positive cells dramatically decreased during the postpartum period. Furthermore, 5 months old 5xFAD transgenic mice that also nursed their offsprings for 4 weeks had a similar Aβ plaque load than merely pregnant mice, indicating that pregnancy alone is sufficient to elevate Aβ plaque levels. Interestingly, housing in an enriched environment reduced the Aβ plaque load and vivified neurogenesis. Our results suggest that pregnancy alters Aβ plaque deposition in 5xFAD transgenic mice and diminishes the generation of newborn neurons. We conclude that pregnancy alone is sufficient to induce this phenotype that can be reversed upon environmental enrichment.