Cerebral blood flow and cerebrovascular reactivity are preserved in a mouse model of cerebral microvascular amyloidosis

Impaired cerebrovascular function is an early biomarker for cerebral amyloid angiopathy (CAA), a neurovascular disease characterized by amyloid-b accumulation in the cerebral vasculature, leading to stroke and dementia. The transgenic Swedish Dutch Iowa (Tg-SwDI) mouse model develops cerebral microvascular amyloid-b deposits, but whether this leads to similar functional impairments is incompletely understood. We assessed cerebrovascular function longitudinally in Tg-SwDI mice with arterial spin labeling (ASL)-magnetic resonance imaging (MRI) and laser Doppler flowmetry (LDF) over the course of amyloid-b deposition. Unexpectedly, TgSwDI mice showed similar baseline perfusion and cerebrovascular reactivity estimates as agematched wild-type control mice, irrespective of modality (ASL or LDF) or anesthesia (isoflurane or urethane and a-chloralose). Hemodynamic changes were, however, observed as an effect of age and anesthesia. Our findings contradict earlier results obtained in the same model and question to what extent microvascular amyloidosis as seen in Tg-SwDI mice is representative of cerebrovascular dysfunction observed in CAA patients.

Automated summary

In the Tg-SwDI mouse model, despite the presence of cerebral microvascular amyloid-b deposits, baseline perfusion and cerebrovascular reactivity estimates were similar compared to age-matched wild-type control mice, regardless of the modality (ASL or LDF) or anesthesia (isoflurane or urethane and a-chloralose). Hemodynamic changes were observed as an effect of age and anesthesia, raising questions about the representativeness of microvascular amyloidosis in Tg-SwDI mice for cerebrovascular dysfunction in CAA patients.