Histopathological correlates of MRI-visible perivascular spaces in cerebral amyloid angiopathy.

本研究涉及脑淀粉样血管病(CAA)患者血管周围间隙扩大的MRI引导病理分析，CAA是CSVD最常见的形式之一。血管周围间隙(PVS)是脑血管周围充满液体的间隙，扩大后可在T2加权MRI上看到，构成CSVD的标志。PVS的扩大以前曾被认为是间隙损害的结果。事实上，PVS与清除大脑中的蛋白质密切相关。越来越多的证据表明，血管周围沿血管壁的清除功能障碍会导致代谢废物从大脑中有缺陷地清除，包括淀粉样蛋白(Aβ)。在CAA中，一种可能的机制是Aβ积聚导致皮质血管的清除障碍，从而导致相同血管下游部分的PVS增大。因此，该项目的主要研究目标是通过在MRI引导下对CAA患者进行详细的EPVS组织病理学检查来验证这一假说。通过这项工作，我们的目标是深入了解A在CAA中的清除机制，这可能对理解血管和阿尔茨海默病病理之间的相互作用产生影响。

The project presented here concerns the MRI-guided pathological analysis of enlarged perivascular spaces (EPVS) in patients with cerebral amyloid angiopathy (CAA), one of the most common forms of CSVD. Perivascular spaces (PVS) are fluid-filled spaces surrounding the brain vessels, that are visible on T2-weighted MRI when enlarged and constitute a hallmark of CSVD. The enlargement of the PVS has previously been suggested to be the result of clearance impairment. In fact, PVS are strongly implicated in the clearance of proteins from the brain. Increasing evidence exists that a dysfunction of the perivascular clearance alongside the walls of vessels leads to a defected removal of metabolic waste from the brain, including Amyloid  (Aβ). In CAA, a possible mechanism is that clearance impairment in the cortical vessels due to Aβ accumulation leads to a clearance block and thus enlargement of PVS in the downstream portion of the same vessels. The overarching research aim of this project is therefore to test this hypothesis, using detailed MRI-guided histopathological examination of EPVS in CAA patients. With this work, we aim to gain insight in the clearance mechanisms of A in CAA, which could have repercussions in understanding the interactions between vascular and Alzheimer’s pathology.