Involvement of the glymphatic/meningeal lymphatic system in Alzheimer's disease: insights into proteostasis and future directions

Cell Mol Life Sci. 2024 Apr 23;81(1):192. doi: 10.1007/s00018-024-05225-z.

Abstract

Background: Alzheimer's disease (AD) is pathologically characterized by the abnormal accumulation of Aβ and tau proteins. There has long been a keen interest among researchers in understanding how Aβ and tau are ultimately cleared in the brain. The discovery of this glymphatic system introduced a novel perspective on protein clearance and it gained recognition as one of the major brain clearance pathways for clearing these pathogenic proteins in AD. This finding has sparked interest in exploring the potential contribution of the glymphatic/meningeal lymphatic system in AD. Furthermore, there is a growing emphasis and discussion regarding the possibility that activating the glymphatic/meningeal lymphatic system could serve as a novel therapeutic strategy against AD.

Objectives: Given this current research trend, the primary focus of this comprehensive review is to highlight the role of the glymphatic/meningeal lymphatic system in the pathogenesis of AD. The discussion will encompass future research directions and prospects for treatment in relation to the glymphatic/meningeal lymphatic system.

Keywords: Brain waster clearance; CNS lymphatics; CSF; ISF; Neurodegenerative diseases.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides* / metabolism
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Glymphatic System* / metabolism
  • Glymphatic System* / pathology
  • Humans
  • Lymphatic System / metabolism
  • Lymphatic System / pathology
  • Meninges* / metabolism
  • Meninges* / pathology
  • Proteostasis*
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • tau Proteins