Impaired cerebrovascular reactivity is associated with vascular smooth muscle cell loss in a mouse model of Alzheimer’s disease

Motivation: Mixed etiology involving AD and vascular issues is a common finding in clinics. However, the underlying mechanism of vascular dysfunction in AD remained to be fully understood. Goal(s): We aim to examine cerebrovascular reactivity (CVR) in an AD model and explore biological underpinnings with histology. Approach: CVR was assessed by a hypercapnia challenge with phase-contrast (PC) and arterial-spin-labeling (ASL) MRI in 9-month-old 5xFAD mice. Immunofluorescent staining was performed to examine amyloid-plaque deposits and vascular-smooth-muscle-cell (VSMC) densities. Results: 5xFAD mice exhibit impaired CVR in the hippocampus, which is associated with microhemorrhage and VSMC loss. Parenchymal amyloid plaque deposits alone are insufficient to jeopardize CVR. Impact: Impaired cerebral vascular reactivity (CVR) is associated with the loss of vascular smooth muscle cells in the hippocampus of 5xFAD model at 9 months of age.