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bioRxiv · 10.64898/2026.08.29.746901

Stroke and Alzheimer's disease have distinct consequences on neurovascular function but synergize to increase amyloid deposition

Ismail, O.·Woodruff, S. S.·Zimmerman, B.·Zhang, W.·Stackhouse, T. L.·Pike, M. M.·Woltjer, R. L.·Mishra, A.
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Abstract

INTRODUCTION: We examined whether stroke induces chronic cerebrovascular dysfunction and thereby exacerbates A{beta} pathology. METHODS: We exposed Tg2576 mice to a transient mild subcortical ischemia and examined cerebrovascular function at chronic timepoints as well as reactive astrocytes and A{beta} deposition post-mortem. RESULTS: Baseline cerebral blood flow and cerebrovascular reactivity (CVR) are both influenced by anesthesia regimen. A{beta} strongly impairs CVR at earlier ages, while mild ischemia impairs CVR at later ages. Mild ischemia reduces neurovascular coupling more strongly than A{beta} and synergistically increases A{beta} deposition in Tg2576 mice. DISCUSSION: Stroke-induced cerebrovascular dysfunction and astrocyte reactivity persist for long periods after the injury. Although there is variability in the spatiotemporal progression of ischemia- and A{beta}-induced vascular impairments, they generally follow the pattern of Thal staging. Surprisingly, the ischemia+A{beta} group showed the least cerebrovascular dysfunction yet an exacerbation of A{beta} deposition, suggesting that these pathologies are connected but not tightly coupled.

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Ismail, O., Woodruff, S. S., Zimmerman, B., Zhang, W., Stackhouse, T. L., Pike, M. M., Woltjer, R. L., Mishra, A.. 2026-09-03. Stroke and Alzheimer's disease have distinct consequences on neurovascular function but synergize to increase amyloid deposition. https://doi.org/10.64898/2026.08.29.746901

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