Temporal Characterization of the Amyloidogenic APP/PS1dE9;hAPOE4 Mouse Model of Alzheimer’s Disease

The development of immunotherapies against Aβ is burdened by clinical adverse events (AEs) observed as amyloid‐related imaging abnormalities (ARIA) on magnetic resonance imaging scans. The vascular inflammatory AEs have been reported in AD clinical trials administrating certain anti‐Aβ plaque‐binding antibodies and are thought to represent cerebral microhemorrhages and vasogenic edema. ARIA incidence appears apolipoprotein (APOE) genotype‐dependent, wherein APOE E4 allele carriers are at higher risk when compared to non‐carriers. With hopes to robustly model patients most at risk for the vascular complications of anti‐Aβ immunotherapy, we selected a relatively new transgenic mouse model bearing the human APOE E4 gene. The model has not yet been extensively characterized at multiple age points. To assess the face validity of the mouse model, we are conducting a battery of histological and biochemical tests.