Vascular amyloidβ load in the meningeal arterial network correlates with loss of cerebral blood flow and pial collateral vessel enlargement in the J20 murine model of Alzheimer's disease

Global reduction in cerebral blood flow (CBF) is an early pathology in Alzheimer's disease, preceding significant plaque accumulation and neurological decline. Chronic reduced CBF and subsequent reduction in tissue oxygenation and glucose may drive neurodegeneration, yet the underlying cause of globally reduced CBF remains unclear. Using premortem delivery of Methoxy-XO4 to label Aβ, and arterial vascular labeling, we assessed Aβ burden on the pial artery/arteriole network and cerebral blood flow in aged male and female WT and J20 AD mice. The pial artery/arteriole vascular network selectively displayed extensive vascular Aβ burden. Pial collateral arteriole vessels, the by-pass system that reroutes blood flow during occlusion, displayed significant enlargement in J20 mice. Despite this, CBF was decreased by approximately 15% in 12-month J20 mice when compared to WT littermates. Significant Aβ burden on the meningeal arterial network may contribute to the restriction of CBF. Redistribution of CBF through enlarged pial collateral vessels may serve as a compensatory mechanism to alter CBF during disease progression in cases of CAA.