Assessment of sex-related neuropathology and cognitive deficits in the Tg-SwDI mouse model of Alzheimer's disease

Cerebral amyloid angiopathy or CAA is a type of vascular dementia that can cause neuroinflammation, ischemia and hemorrhage, among other complications. CAA results from the deposition of amyloid beta (A beta) in blood vessels and is frequently observed in individuals with Alzheimer's disease (AD). One functional output of those pathological changes is measurable cognitive decline. Still not well understood, however, is the impact of gender or sex on the pathology of CAA, as well as CAA-induced cognitive decline. Here, we studied how sex impacts deposition of CAA-related pathology and the associated cognitive decline. We observed differential hippocampal pathology as far as regions of deposition, type of morphology, and total amount of pathology when assessing CAA pathology via (E,E)-1-fluoro-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (FSB)-labeling, as well as neurodegeneration via Fluoro Jade C (FJC)-labeling, and lysosomal associated membrane protein deposition via LAMP-1 labeling. In accordance with other studies, our data suggest female TG-SwDI mice exhibit more severe pathological alterations in CAA pathology. Additionally, behavioral assessments revealed an impact of genotype that was more pronounced in TG-SwDI females. While the primary measure of learning and memory, the water maze, suggests an overall effect of genotype, effects in measures of locomotor activity and anxiety-like behavior suggest reduced habituation in females. This could be due to a lower retention for the tasks. Results of this study offer significant insight into the importance of examining effects of sex on CAA.