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


Princz-Kranz, F L; Mueggler, T; Knobloch, M; Nitsch, R M; Rudin, M (2010). Vascular response to acetazolamide decreases as a function of age in the arcA beta mouse model of cerebral amyloidosis. Neurobiology of Disease, 40(1):284-292.

Abstract

Deposition of beta-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 arcA beta mice. In a cortical brain region of interest (ROI), displaying high CAA, arcA beta 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 arcA beta and wild-types. These findings indicate that vascular beta-amyloid deposits reduce the capacity of cerebral blood vessels to dilate upon demand, supporting the hypothesis that vascular beta-amyloid contributes to hypoperfusion and neurological deficits observed in AD and CAA. High diagnostic accuracy of the combined readouts in detecting vascular dysfunction in arcA beta mice was found.

Abstract

Deposition of beta-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 arcA beta mice. In a cortical brain region of interest (ROI), displaying high CAA, arcA beta 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 arcA beta and wild-types. These findings indicate that vascular beta-amyloid deposits reduce the capacity of cerebral blood vessels to dilate upon demand, supporting the hypothesis that vascular beta-amyloid contributes to hypoperfusion and neurological deficits observed in AD and CAA. High diagnostic accuracy of the combined readouts in detecting vascular dysfunction in arcA beta mice was found.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology

04 Faculty of Medicine > Institute of Biomedical Engineering
04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:570 Life sciences; biology
170 Ethics
610 Medicine & health
Language:English
Date:2010
Deposited On:14 Dec 2010 13:20
Last Modified:16 Aug 2016 10:13
Publisher:Elsevier
ISSN:0969-9961
Publisher DOI:https://doi.org/10.1016/j.nbd.2010.06.002
PubMed ID:20600914

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