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- Title
Age-dependent cerebrovascular dysfunction in a transgenic mouse model of cerebral amyloid angiopathy.
- Authors
Hwa Kyoung Shin; Phillip B. Jones; Monica Garcia-Alloza; Laura Borrelli; Steven M. Greenberg; Brian J. Bacskai; Matthew P. Frosch; Bradley T. Hyman; Michael A. Moskowitz; Cenk Ayata
- Abstract
The Tg2576 transgenic mouse model of human cerebral amyloid angiopathy is characterized by age-dependent cerebrovascular deposition of amyloid-β (Aβ) starting from 9 months of age and progressively worsening to involve most pial arterioles by 18 months; soluble Aβ levels are elevated long before vascular deposition takes place in this model. It has been suggested that elevated soluble Aβ levels alone are sufficient to impair cerebral blood flow (CBF) regulation thereby contributing to the early progression of Alzheimers disease. Using laser speckle flowmetry through an intact skull, we studied the impact of elevated soluble Aβ levels and vascular Aβ deposition on a wide range of CBF responses to evaluate vasodilation and vasoconstriction in young or aged Tg2576 mice. Nineteen-month-old Tg2576 with severe vascular Aβ deposits showed an attenuated hyperaemic response during hypercapnia and whisker stimulation compared to wild-type littermates. The anticipated increase in CBF due to isoflurane anaesthesia was also suppressed, as were the typical hypoperfusion responses during cortical spreading depression and α-chloralose anaesthesia. The responses of 8-month-old Tg2576 with elevated soluble Aβ levels, but without vascular Aβ deposition, did not differ from age-matched controls. In conclusion, our data suggest that vascular Aβ deposition is associated with impaired vasodilator as well as vasoconstrictor responses to a wide range of stimuli. These responses do not differ from controls when studied non-invasively prior to vascular Aβ deposition, thus challenging the view that elevated soluble Aβ levels are sufficient to cause cerebrovascular dysfunction.
- Publication
Brain: A Journal of Neurology, 2007, Vol 130, Issue 9, p2310
- ISSN
0006-8950
- Publication type
Academic Journal
- DOI
10.1093/brain/awm156