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

We examined whether stroke induces chronic cerebrovascular dysfunction and thereby exacerbates Aβ pathology.

We exposed Tg2576 mice to a transient mild subcortical ischemia and examined cerebrovascular function at chronic timepoints as well as reactive astrocytes and Aβ deposition post-mortem.

Baseline cerebral blood flow and cerebrovascular reactivity (CVR) are both influenced by anesthesia regimen. Aβ strongly impairs CVR at earlier ages, while mild ischemia impairs CVR at later ages. Mild ischemia reduces neurovascular coupling more strongly than Aβ and synergistically increases Aβ deposition in Tg2576 mice.

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 Aβ-induced vascular impairments, they generally follow the pattern of Thal staging. Surprisingly, the ischemia+Aβ group showed the least cerebrovascular dysfunction yet an exacerbation of Aβ deposition, suggesting that these pathologies are connected but not tightly coupled.