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September 17, 2025

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

Key Points

Impaired cerebrovascular reactivity was found in 5xFAD mice, correlating with vascular smooth muscle cell loss.
In the hippocampus, CVR impairment was linked to microhemorrhage, indicating significant vascular alterations.
Hypercapnia challenge and MRI techniques were utilized to evaluate cerebrovascular reactivity and observe histological changes.
The findings highlight vascular dysfunction's role in Alzheimer's disease, warranting further investigation into underlying mechanisms.

Abstract

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.

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

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