Taken together, the findings of our study, in young cognitively healthy 4- to 5-month-old APP/PS1 mice with a low number of parenchymal amyloid plaques with no CAA, reveal early pathological changes to the cerebral cortical capillaries, hepatic sinusoidal vessels, splenic venous sinuses in addition to impairments in renal albumin clearance that may be early indicators of progression to severe disease in this experimental AD murine model. This evidence concerns the gene APP and Alzheimer disease.