Winkler D T, Bondolfi L, Herzig M C, Jann L, Calhoun M E, Wiederhold K H, Tolnay M, Staufenbiel M, Jucker M
Department of Neuropathology, Institute of Pathology, University of Basel, CH-4003 Basel, Switzerland.
J Neurosci. 2001 Mar 1;21(5):1619-27. doi: 10.1523/JNEUROSCI.21-05-01619.2001.
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.
脑淀粉样血管病（CAA）是自发性且常致命的脑叶出血的一个高风险因素。我们现在报告，在淀粉样前体蛋白转基因小鼠模型（APP23小鼠）中，CAA会导致血管平滑肌细胞丧失、动脉瘤样血管扩张，在罕见情况下还会导致血管闭塞和严重血管炎。血管壁的这种削弱随后会引发破裂和出血，范围从多发性复发性微出血到大型血肿。我们的结果表明，在APP转基因小鼠中，神经元衍生的β-淀粉样蛋白在血管壁中的细胞外沉积是血管壁破坏的原因，最终导致实质出血。这个首个与CAA相关的出血性中风小鼠模型现在将有助于开发诊断和治疗策略。
