Reduced activity in a brain region called the retrosplenial cortex is linked to sex-dependent vulnerability in Alzheimer’s disease
Alzheimer’s disease (AD) occurs more often and progresses faster in women than men. Understanding the causes of these sex differences will help us to better understand the pathobiology of the disease. Here, Dylan Terstege, working in the laboratory of Jonathan Epp at the University of Calgary, identified a novel, sex-dependent vulnerability in a brain region called the retrosplenial cortex (RSC) that links dysfunction of a specific brain cell-type, parvalbumin interneurons (PV-interneurons), to early cognitive decline in Alzheimer’s disease. Using a mouse model of Alzheimer’s disease (called 5xFAD mice), the researchers noted that female but not male 5xFAD mice exhibited early reduced metabolic activity and higher excitability in the RSC brain region.
Read the scientific article:
Terstege, D. J., Ren, Y., Ahn, B. Y., Seo, H., Adigun, K., Alzheimer’s Disease Neuroimaging Initiative, Galea, L. A. M., Sargin, D., Epp, J. R. (2025). Impaired parvalbumin interneurons in the retrosplenial cortex as the cause of sex-dependent vulnerability in Alzheimer’s disease. Science Advances, 11(18), eadt8976.
