Vascular response to acetazolamide decreases as a function of age in the arcAβ mouse model of cerebral amyloidosis

Abstract

Deposition of β-amyloid along cerebral vessels is found in most patients suffering from Alzheimer's disease. The effects of cerebral amyloid angiopathy (CAA) on the function of cerebral blood vessels were analyzed applying cerebral blood volume (CBV)-based fMRI to transgenic arcAβ mice. In a cortical brain region of interest (ROI), displaying high CAA, arcAβ mice older than 16 months showed reduced response to the vasodilatory substance acetazolamide compared to age-matched wild-type animals, both with regard to rate (vascular reactivity) and extent of vasodilation (maximal vasodilation). In a subcortical ROI, displaying little CAA, no genotype-specific decrease was observed, but maximal vasodilation decreased with age in arcAβ and wild-types. These findings indicate that vascular β-amyloid deposits reduce the capacity of cerebral blood vessels to dilate upon demand, supporting the hypothesis that vascular β-amyloid contributes to hypoperfusion and neurological deficits observed in AD and CAA. High diagnostic accuracy of the combined readouts in detecting vascular dysfunction in arcAβ mice was found.

Keywords

• Acetazolamide
• Alzheimer's disease (AD)
• Cerebral amyloid angiopathy (CAA)
• Cerebral blood volume (CBV)
• Functional magnetic resonance imaging (fMRI)
• Transgenic mouse model