Spontaneous hemorrhagic stroke in a mouse model of cerebral amyloid angiopathy

A high risk factor for spontaneous and often fatal lobar hemorrhage is cere bral amyloid angiopathy (CAA). We now report that CAA in an amyloid precurs or protein transgenic mouse model (APP23 mice) leads to a loss of vascular smooth muscle cells, aneurysmal vasodilatation, and in rare cases, vessel o bliteration and severe vasculitis. This weakening of the vessel wall is fol lowed by rupture and bleedings that range from multiple, recurrent microhem orrhages to large hematomas. Our results demonstrate that, in APP transgeni c mice, the extracellular deposition of neuron-derived beta -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 hemorr hagic stroke will now allow development of diagnostic and therapeutic strat egies.