Mouse female hippocampus proteomics of Alzheimer Tg-SwDI Model

Cerebral Amyloid Angiopathy (CAA) is a significant comorbidity in almost all cases of Alzheimer’s disease (AD) and is unaddressed by current treatment regimens. We explored the Tg-SwDI mouse model which expresses human Amyloid Precursor Protein with the familial Swedish AD mutation as well as the vasculotropic Dutch and Iowa mutations leading to a phenotype of cognitive deficits with severe CAA. This is the first mapping of cerebral parenchymal proteomes of this model. In a cohort of presymptomatic mice both the cortex and hippocampus proteomes were mapped in male as well as female mice. In the four proteomes profound adaptations were identified, and previous findings of an early and severe pathology in Tg-SwDI female mice are reaffirmed on the molecular level. In addition, the effectiveness of two Carbonic Anhydrase Inhibitors (CAIs), Acetazolamide and Methazolamide, in preventing the observed molecular adaptations was evaluated. These repurposed drugs broadly prevented the proteome adaptations in the Tg-SwDI mice.