Cerebral amyloid angiopathy is associated with glymphatic transport reduction and time-delayed solute drainage along the neck arteries

Cerebral amyloid angiopathy (CAA) is a common disease in older adults that contributes to dementia^1–3. In CAA, amyloid beta (Aβ) is deposited along either capillaries (type 1) or vessel walls (type 2)⁴, with the underlying pathophysiology incompletely understood⁵. Here, we developed imaging and analysis tools based on regularized optimal mass transport (rOMT) theory^6,7 to characterize cerebrospinal fluid (CSF) flow dynamics and glymphatic transport in a transgenic CAA type 1 rat model. We discovered that, in CAA, CSF moves more rapidly along the periarterial spaces that serve as influx routes to the glymphatic system. The observation of high-speed CSF flow currents in CAA was unexpected given the build-up of microvascular Aβ. However, velocity flux vector analysis revealed that CSF currents in CAA are partly diverted away from the brain, resulting in overall decreased glymphatic transport. Imaging at the neck showed that drainage to the deep cervical lymph nodes occurs along the carotid arteries and is time delayed in CAA, implying that upstream connections to the meningeal lymphatics were altered. Based on our findings we propose that, in CAA, both glymphatic transport and lymphatic drainage are compromised and that both systems represent therapeutic targets for treatment of CAA-related cognitive decline and dementia.