Sporadic cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular amyloid beta (Aβ) deposits and causes cerebral hemorrhage and dementia. The exact molecules that co-accumulate with cerebrovascular Aβ deposits are still not fully known. In our study here, we performed proteomic analyses with microdissected leptomeningeal arteries and cerebral neocortical arterioles from 8 cases with severe CAA, 12 cases with mild CAA, and 10 control cases without CAA, and we determined the levels of highly expressed proteins in cerebral blood vessels in CAA. We focused on sushi repeat-containing protein 1 (SRPX1), which is specifically expressed in CAA-affected cerebral blood vessels. Because SRPX1, which is known as a tumor suppressor gene, reportedly induced apoptosis in tumor cells, we hypothesized that SRPX1 may play an important role in Aβ-induced apoptosis in CAA. Immunohistochemical studies revealed that SRPX1 co-accumulated with Aβ deposits in cerebral blood vessels of all autopsied cases with severe CAA. In contrast, no SRPX1 co-accumulated with Aβ deposits in senile plaques. Furthermore, we demonstrated that both Aβ40 and Aβ42 bound to SRPX1 in vitro and enhanced SRPX1 expression in primary cultures of cerebrovascular smooth muscle cells. SRPX1 enhanced caspase activity induced by Aβ40. Knockdown of SRPX1, in contrast, reduced the formation of Aβ40 accumulations and the activity of caspase in cultured cerebrovascular smooth muscle cells. SRPX1 may thus be a novel molecule that is up-regulated in cerebrovascular Aβ deposits and that may increase Aβ-induced cerebrovascular degeneration in CAA.

散发性脑淀粉样血管病（CAA）的特征是脑血管淀粉样β（Aβ）沉积，并引起脑出血和痴呆。与脑血管Aβ沉积物共同积聚的确切分子仍不完全清楚。在我们的研究中，我们对8例重度CAA，12例轻度CAA和10例无CAA的细小脑膜小动脉和大脑新皮层小动脉进行了蛋白质组学分析，并确定了脑血管中高表达蛋白的水平在CAA中。我们专注于含寿司重复序列的蛋白1（SRPX1），该蛋白在受CAA影响的脑血管中特异性表达。由于据称是抑癌基因的SRPX1诱导了肿瘤细胞的凋亡，我们假设SRPX1可能在Aβ诱导的CAA细胞凋亡中起重要作用。免疫组织化学研究表明，在所有患有严重CAA的尸检病例中，SRPX1与Aβ沉积物共同积聚在脑血管中。相反，在老年斑中没有SRPX1与Aβ沉积物共同积聚。此外，我们证明Aβ40和Aβ42都在体外与SRPX1结合，并在脑血管平滑肌细胞的原代培养物中增强了SRPX1的表达。SRPX1增强了Aβ40诱导的caspase活性。相比之下，SRPX1的敲低减少了培养的脑血管平滑肌细胞中Aβ40积累的形成和caspase的活性。因此，SRPX1可能是在脑血管Aβ沉积物中上调的新型分子，并可能增加CAA中Aβ诱导的脑血管变性。免疫组织化学研究表明，在所有患有严重CAA的尸检病例中，SRPX1与Aβ沉积物共同积聚在脑血管中。相反，在老年斑中没有SRPX1与Aβ沉积物共同积聚。此外，我们证明Aβ40和Aβ42都在体外与SRPX1结合，并在脑血管平滑肌细胞的原代培养物中增强了SRPX1的表达。SRPX1增强了Aβ40诱导的caspase活性。相比之下，SRPX1的敲低减少了培养的脑血管平滑肌细胞中Aβ40积累的形成和caspase的活性。因此，SRPX1可能是在脑血管Aβ沉积物中上调的新型分子，并可能增加CAA中Aβ诱导的脑血管变性。免疫组织化学研究表明，在所有患有严重CAA的尸检病例中，SRPX1与Aβ沉积物共同积聚在脑血管中。相反，在老年斑中没有SRPX1与Aβ沉积物共同积聚。此外，我们证明Aβ40和Aβ42都在体外与SRPX1结合，并在脑血管平滑肌细胞的原代培养物中增强了SRPX1的表达。SRPX1增强了Aβ40诱导的caspase活性。相比之下，SRPX1的敲低减少了培养的脑血管平滑肌细胞中Aβ40积累的形成和caspase的活性。因此，SRPX1可能是在脑血管Aβ沉积物中上调的新型分子，并可能增加CAA中Aβ诱导的脑血管变性。