Small vessel disease and Alzheimer's disease ; the glymphatic pathway in amyloid beta clearance system

Abstract

Alzheimer's disease is a most common form of dementia and clinically characterized by progressive decline of cognitive function. The key hallmarks for the diagnosis of Alzheimer's disease are the accumulation of amyloid–β (Aβ) peptide into extracellular plaques and tau associated neurofibrillary tangles. There has been complicated mechanism in the development of Alzheimer's disease. Abnormal aggregates and accumulation of Aβ has been one of the most important mechanisms. Several clearance mechanisms in the brain have been assumed for Aβ excretion. There are two major type of clearance system through cerebrospinal fluid (CSF) and interstitial fluid (ISF), which are divided into perivascular drainage pathway and glymphatic pathway. CSF flows through the periarterial space and across the astroglial endfeet which express aquaporin 4 (AQP4) channels. Mixed CSF and ISF are driven into the perivenous space. Recently, the glymphatic pathway has been noted, and further implicated that the glymphatic function can be related pathologically to Alzheimer's disease. Amyloid β is deposited in the vascular smooth muscle cell layer in cerebral amyloid angiopathy (CAA), and CAA is closely associated with Alzheimer's disease. This close association might be attributable to the dysfunction of glymphatic system. Understanding the mechanism of glymphatic pathway might be pivotal to explore for the pathogenesis of Alzheimer's disease.