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Brain. 2007 Sep;130(Pt 9):2310-9. Epub 2007 Jul 16.

Age-dependent cerebrovascular dysfunction in a transgenic mouse model of cerebral amyloid angiopathy.

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  • 1Stroke and Neurovascular Regulation Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.


The Tg2576 transgenic mouse model of human cerebral amyloid angiopathy is characterized by age-dependent cerebrovascular deposition of amyloid-beta (Abeta) starting from 9 months of age and progressively worsening to involve most pial arterioles by 18 months; soluble Abeta levels are elevated long before vascular deposition takes place in this model. It has been suggested that elevated soluble Abeta levels alone are sufficient to impair cerebral blood flow (CBF) regulation thereby contributing to the early progression of Alzheimer's disease. Using laser speckle flowmetry through an intact skull, we studied the impact of elevated soluble Abeta levels and vascular Abeta 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 Abeta 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 alpha-chloralose anaesthesia. The responses of 8-month-old Tg2576 with elevated soluble Abeta levels, but without vascular Abeta deposition, did not differ from age-matched controls. In conclusion, our data suggest that vascular Abeta 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 Abeta deposition, thus challenging the view that elevated soluble Abeta levels are sufficient to cause cerebrovascular dysfunction.

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