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Previous Article | Next Article
The Journal of Neuroscience, March 1, 2001, 21(5):1619-1627
Spontaneous Hemorrhagic Stroke in a Mouse Model of Cerebral Amyloid Angiopathy
David T. Winkler1, Luca Bondolfi1, Martin C. Herzig1, Lukas Jann1, Michael E. Calhoun1, 2, Karl-Heinz Wiederhold3, Markus Tolnay1, Matthias Staufenbiel3, and Mathias Jucker1 1 Department of Neuropathology, Institute of Pathology, University of Basel, CH-4003 Basel, Switzerland, 2 Kastor Neurobiology of Aging Laboratories, Mount Sinai School of Medicine, New York, New York 10029, and 3 Nervous System Research, Novartis Pharma Ltd., CH-4002 Basel, Switzerland
A high risk factor for spontaneous and often fatal lobar hemorrhage is cerebral amyloid angiopathy (CAA). We now report that CAA in an amyloid precursor protein transgenic mouse model (APP23 mice) leads to a loss of vascular smooth muscle cells, aneurysmal vasodilatation, and in rare cases, vessel obliteration and severe vasculitis. This weakening of the vessel wall is followed by rupture and bleedings that range from multiple, recurrent microhemorrhages to large hematomas. Our results demonstrate that, in APP transgenic mice, the extracellular deposition of neuron-derived
-amyloid in the vessel wall is the cause of vessel wall disruption, which eventually leads to parenchymal hemorrhage. This first mouse model of CAA-associated hemorrhagic stroke will now allow development of diagnostic and therapeutic strategies.
Key words: cerebral amyloid angiopathy; hemorrhage; stroke; bleeding; Alzheimer's disease; amyloid; amyloid precursor protein; smooth muscle cells; mouse; brain; CNS
Copyright © 2001 Society for Neuroscience 0270-6474/01/2151619-09$05.00/0
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