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Updated: Jun 18, 2026

A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis
Published on: November 22, 2024
WSB.APP/PS1 mice develop age-dependent cerebral amyloid angiopathy, cerebrovascular dysfunction, and white matter
Olivia J Marola1, Asli Uyar2, Kelly J Keezer1
1The Jackson Laboratory, Bar Harbor, Maine, USA.
Introduction:
Cerebrovascular deficits, including cerebral amyloid angiopathy (CAA), play a key role in Alzheimer's disease (AD) pathogenesis. Here, we characterize the susceptibility of the WSB/EiJ genetic context to human AD-relevant cerebrovascular phenotypes.
Methods:
CAA and parenchymal plaque analysis and in vivo neurovascular imaging were performed on WSB.APP/PS1 brains. Transcriptomics was performed on WSB.APP/PS1 and B6.APP/PS1 brains. B6 and WSB cerebrovascular reactivity was assayed ex vivo. Additional CAA and parenchymal plaque analysis was performed on WSB.APP/PS1 mice with APOE2, APOE3, or APOE4 alleles.
Results:
WSB.APP/PS1 brains exhibited plaque deposition, CAA, transcriptomic overlap with human AD, myelin deficits, cerebrovascular/metabolic uncoupling, and altered cerebrovascular morphology. Aged WSB vasculature retained vasoreactivity but exhibited increased stiffness. Compared to WSB.APOE2/2APP/PS1, WSB.APOE4/4APP/PS1 mice had increased CAA and plaque-associated microglial area.
Discussion:
These data illustrate the utility of the WSB genetic context to model CAA and uncover vascular contributions to AD.
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