ApoE4-mediated blood-brain barrier damage in Alzheimer's disease: Progress and prospects

Brain Res Bull. 2023 Jul:199:110670. doi: 10.1016/j.brainresbull.2023.110670. Epub 2023 May 22.

Abstract

Late-onset Alzheimer's disease (AD), a neurodegenerative disease, is expected in the elderly population and adversely affects families and society. The extensive debate on the deposition of amyloid (Aβ), abnormal phosphorylation of Tau protein, and neuroinflammation hypothesis in the pathogenesis of AD has been recognized by many scholars. The blood-brain barrier (BBB) is an essential physical barrier that protects the brain from external material interference, and its integrity affects the process of AD. Apolipoprotein E4 (ApoE4) has shown a critical regulatory role in many studies and is a crucial protein that affects AD. Numerous current studies on ApoE4 are based on complementary hypotheses to the three hypotheses above, ignoring the effect of ApoE4 on BBB constitutive cells and the role of the BBB in AD. In this review, we summarize the findings of the role of ApoE4 in the composition of the BBB and the value of ApoE4 for maintaining BBB integrity, which may play an essential role in changing the progression of the disease.

Keywords: Alzheimer's Disease; Apolipoprotein E4; Astrocytes; Blood Brain Barrier; Cerebral Vascular Endothelial Cells; Pericyte.

Publication types

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

MeSH terms

  • Aged
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Apolipoprotein E4 / genetics
  • Blood-Brain Barrier / metabolism
  • Brain / metabolism
  • Humans
  • Neurodegenerative Diseases* / pathology

Substances

  • Apolipoprotein E4
  • Amyloid beta-Peptides