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

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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.