title: Vascular response to acetazolamide decreases as a function of age in the arcA beta mouse model of cerebral amyloidosis.
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.
authors.affiliation: Institute for Biomedical Engineering, University and ETH Zurich, Switzerland.
authors.forename: Felicitas L
authors.initials: FL
authors.lastname: Princz-Kranz
authors.forename: Thomas
authors.initials: T
authors.lastname: Mueggler
authors.forename: Marlen
authors.initials: M
authors.lastname: Knobloch
authors.forename: Roger M
authors.initials: RM
authors.lastname: Nitsch
authors.forename: Markus
authors.initials: M
authors.lastname: Rudin
mesh_terms: D000086:Acetazolamide; D000375:Aging / Q000187:drug effects / Q000235:genetics*; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D016657:Cerebral Amyloid Angiopathy / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D005819:Genetic Markers; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011237:Predictive Value of Tests; D014665:Vasodilator Agents
chemical_list: D016564:Amyloid beta-Protein Precursor; D005819:Genetic Markers; D014665:Vasodilator Agents; D000086:Acetazolamide