Kara Jo Swafford, MD

Freeze WM, Bacskai BJ, Frosch MP, Jacobs HIL, Backes WH, Greenberg SM, et al. Blood-Brain Barrier Leakage and Microvascular Lesions in Cerebral Amyloid Angiopathy. Stroke. 2019;50:328–335.

Cerebral amyloid angiopathy (CAA) is characterized by amyloid-b (Ab) deposition within walls of small to medium sized arteries, arterioles and capillaries in the cerebral cortex and leptomeninges. It is observed in approximately 33% of the general aged population and 90% of those with Alzheimer’s disease. CAA can lead to cerebral microbleeds (CMBs) and cerebral microinfarcts (CMIs), as well as cerebral atrophy, structural network disruption and cognitive decline. In the elderly, CAA is the most common cause of lobar intracerebral hemorrhage.

Freeze et al performed a postmortem study to investigate the role of blood-brain barrier (BBB) disruption in CAA-related brain injury, hypothesizing that BBB leakage is associated with CAA severity and is present predominantly in parietooccipital regions because of CAA’s predilection for affecting blood vessels in these regions. Eleven CAA confirmed cases were compared to 7 controls without neurological disease. BBB disruption was measured by plasma protein (fibrin, IgG) extravasation in the cortex. CAA severity was graded based on presence of Aβ. Microvascular lesions (CMBs, CMIs) were assessed using histopathology and MRI.

There were more extravasated plasma proteins in CAA cases compared to controls, with a posterior predilection in CAA cases, that positively correlated with CAA severity and number of CMBs on MRI. Number of CMBs was not associated with CAA severity, leading to question how vascular Aβ is related to CMB formation. There was no significant association between CMIs and fibrin deposition in tissue or on MRI.

BBB leakage of plasma proteins may provide a biomarker identifying vessels at increased risk of rupture due to CAA and provide a treatment target for prevention or intervention. A strength of this study was use of postmortem confirmed CAA cases utilizing histopathology and MRI to evaluate microvascular lesions. Limitations include small sample size and poor to moderate interrater agreement on vessel involvement.