Cerebral microinfarct is emergency consequence of Alzheimer's disease: a new insight into development of neurodegenerative diseases

Int J Biol Sci. 2022 Jan 24;18(4):1569-1579. doi: 10.7150/ijbs.55419. eCollection 2022.

Abstract

Imbalance of Aβ and tau protein production and clearance are the key factors among many causes of Alzheimer's disease that leading to neurons degeneration and cognitive disorders. As a novel approach, glymphatic system quickly clear metabolic waste (especially Aβ and tau) from cerebral environment, and dysfunction of glymphatic system may relate to occurrence of Alzheimer's disease. Microinfarct is a common histopathologic situation occurring in aging brain and leads to dramatic increase the generation of metabolic by-product after neuronal injury, hindering the operation of glymphatic system and suppress cerebral spinal fluid (CSF) and cerebral interstitial fluid (interstitial fluid, ISF) exchange. Microinfarcts destruct the integrity of microvascular and microstructural tissue, result in Aβ deposition and tau phosphorylation that form neurofibrillary tangles and associated with the cause of Alzheimer's disease. Currently, it has been found that glymphatic system is involved in the pathological process of Alzheimer's disease. Improving the function of glymphatic system after cerebral microinfarcts could be developed as a new approach for Alzheimer's disease prevention and treatment. In this review, we will provide in-depth discussion on functional changes of glymphatic system after cerebral microinfarcts, further reveal pathogenesis of Alzheimer's disease and provide a potentially more effective method for treatment of Alzheimer's disease.

Keywords: AQP4; astrocytes; cognitive dementia; glymphatic; microinfarct.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease* / metabolism
  • Brain / metabolism
  • Glymphatic System* / metabolism
  • Glymphatic System* / pathology
  • Humans
  • Neurodegenerative Diseases* / metabolism
  • Neurons / metabolism