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Neurotoxicity Research

, Volume 34, Issue 3, pp 733–748 | Cite as

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

  • Shu-Hui Xin
  • Lin Tan
  • Xipeng Cao
  • Jin-Tai Yu
  • Lan Tan
REVIEW

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disease. Pathological proteins of AD mainly contain amyloid-beta (Aβ) 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 Aβ and tau in order to delay or even halt AD. Aβ 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 Aβ 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 Aβ clearance. Tau clearance is almost the same as Aβ clearance. In this review, we will mainly introduce the clearance mechanisms of Aβ and tau proteins, and summarize corresponding targeted drug therapies for AD.

Keywords

Alzheimer’s disease Amyloid-beta Tau Blood circulatory clearance Lymphatic clearance Peripheral clearance 

Abbreviations

AD

Alzheimer’s disease

Beta-amyloid

ALS

Autophagy-lysosome system

AQP4

Aquaporin 4

ABCC1

ATP-binding cassette C1

BBB

Blood-brain barrier

BCSFB

Blood-brain barrier

CSF

Cerebrospinal fluid

DHA

Docosahexaenoic acid

EPA

Eicosapentaenoic acid

GULT1

Glucose transporter 1

IDE

Insulin-degrading enzyme

ISF

Interstitial fluid

LRP1

Lipoprotein receptor protein-1

MMPs

Matrix metalloproteinases

NEP

Neprilysin

PICALM

Phosphatidylinositol-binding clathrin assembly protein

P-gp

P-glycoprotein

RAGE

Receptor for advanced glycation end products

RBC

Red blood cell

UPS

Ubiquitin–proteasome system

Notes

Acknowledgments

This work was supported by grants from the National key projects for research and development of MOST (2016YFC1305800), the Shandong Provincial Outstanding Medical Academic Professional Program, Qingdao Key Health Discipline Development Fund, Qingdao Outstanding Health Professional Development Fund, and Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 1.Department of Neurology, Qingdao Municipal Hospital, School of MedicineQingdao UniversityQingdaoChina
  2. 2.Clinical Research Center, Qingdao Municipal HospitalQingdao UniversityQingdaoChina

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