期刊
NEUROBIOLOGY OF DISEASE
卷 40, 期 1, 页码 284-292出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2010.06.002
关键词
Acetazolamide; Alzheimer's disease (AD); Cerebral amyloid angiopathy (CAA); Cerebral blood volume (CBV); Functional magnetic resonance imaging (fMRI); Transgenic mouse model
资金
- Swiss National Science Foundation [SNF 310000-112835, SNF 310030-126029]
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 CM. High diagnostic accuracy of the combined readouts in detecting vascular dysfunction in arcA beta mice was found. (c) 2010 Elsevier Inc. All rights reserved.
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