Objective:

To understand the role of the glymphatic system in the pathogenesis of Alzheimer’s Disease (AD) and Cerebral Amyloid Angiopathy (CAA) to encourage further investigative research focused on restoring glymphatic function to decelerate disease progression.

Background:

Alzheimer’s Disease (AD), the most common form of dementia, is characterized pathologically by the abnormal accumulation of amyloid β (Aβ) and phosphorylated tau (p-Tau). The recent discovery of the glymphatic system offers a potential explanation for Aβ accumulation in AD. Impaired glymphatic flow is also postulated to be responsible for the pathogenesis of CAA to AD.

Design/Methods:

We performed an electronic literature search in PubMed, Google Scholar, and Scopus regarding the glymphatic system, AD, and CAA. We then synthesized common themes, trends, and results into a literature review.

Results:

The recent discovery of the glymphatic system suggests that impaired clearance through aquaporin-4 (AQP4) channels on glial membranes, rather than excessive protein production, may contribute to Aβ accumulation leading to AD. The clearance of Aβ by the glymphatic system is most active during rest but can be impaired by sleep deprivation and cerebral vascular abnormalities such as cerebral amyloid angiopathy (CAA) and subarachnoid hemorrhage (SAH).

Conclusions:

The growing evidence of glymphatic system dysfunction as a contributing factor to AD pathology calls attention to the importance of understanding how impaired CSF fluid dynamics impact disease progression. The glymphatic system’s relationship with sleep deprivation, CAA, and SAH, provide insight into the mechanisms underlying accelerated cognitive decline. Collectively, this emphasizes the need for continued exploration of effective diagnostic and therapeutic strategies for AD.