Spontaneous hemorrhagic stroke in a mouse model of cerebral amyloid angiopathy.
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 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 hemorrhagic stroke will now allow development of diagnostic and therapeutic strategies.
Winkler
D T
DT
Department of Neuropathology, Institute of Pathology, University of Basel, CH-4003 Basel, Switzerland.
Bondolfi
L
L
Herzig
M C
MC
Jann
L
L
Calhoun
M E
ME
Wiederhold
K H
KH
Tolnay
M
M
Staufenbiel
M
M
Jucker
M
M
D000375:Aging / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007178:Inbreeding; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009154:Mutation; D015203:Reproducibility of Results; D020293:Vasculitis, Central Nervous System / Q000150:complications / Q000473:pathology; D014664:Vasodilation
D016564:Amyloid beta-Protein Precursor