Clearance of Amyloid Beta and Tau in Alzheimer's Disease: from Mechanisms to Therapy

Alzheimer's disease (AD) is the most common neurodegenerative disease. Pathological proteins of AD mainly contain amyloid-beta (A beta) and tau. Their deposition will lead to neuron damage by a series of pathways, and then induce memory and cognitive impairment. Thus, it is pivotal to understand the clearance pathways of A beta and tau in order to delay or even halt AD. A beta clearance mechanisms include ubiquitin-proteasome system, autophagy-lysosome, proteases, microglial phagocytosis, and transport from the brain to the blood via the blood-brain barrier (BBB), arachnoid villi and blood-CSF barrier, which can be named blood circulatory clearance. Recently, lymphatic clearance has been demonstrated to play a key role in transport of A beta into cervical lymph nodes. The discovery of meningeal lymphatic vessels is another direct evidence for lymphatic clearance in the brain. Furthermore, periphery clearance also contributes to A beta clearance. Tau clearance is almost the same as A beta clearance. In this review, we will mainly introduce the clearance mechanisms of A beta and tau proteins, and summarize corresponding targeted drug therapies for AD.