A new study by Simon et al delves into the brain changes associated with Alzheimer’s disease, focusing on the APPswe/PSEN1dE9 double transgenic mouse model. Researchers explored how amyloidosis, a condition marked by amyloid plaques in the brain, affects functional network ‘hub’ topology differently in male and female mice. These hubs are critical for brain connectivity and function. Using a combination of fear memory tests, 11.1 Tesla magnetic resonance imaging of brain connectivity, and RNA sequencing, scientists discovered that amyloidosis alters network connectivity and gene expression, particularly in females. Notably, in female mice, certain neuronal genes involved in signaling processes and motor activity were downregulated due to amyloidosis, while immune-related genes were upregulated in both sexes. The findings suggest a link between amyloid presence, connectivity changes, and potential disruptions in non-cognitive brain circuitry, providing insight into the mechanisms behind Alzheimer’s disease and its sex-dependent differences.
