Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-beta peptides

Nat Med. 2004 Jul;10(7):719-26. doi: 10.1038/nm1058. Epub 2004 Jun 13.


We have previously shown that apolipoprotein E (Apoe) promotes the formation of amyloid in brain and that astrocyte-specific expression of APOE markedly affects the deposition of amyloid-beta peptides (Abeta) in a mouse model of Alzheimer disease. Given the capacity of astrocytes to degrade Abeta, we investigated the potential role of Apoe in this astrocyte-mediated degradation. In contrast to cultured adult wild-type mouse astrocytes, adult Apoe(-/-) astrocytes do not degrade Abeta present in Abeta plaque-bearing brain sections in vitro. Coincubation with antibodies to either Apoe or Abeta, or with RAP, an antagonist of the low-density lipoprotein receptor family, effectively blocks Abeta degradation by astrocytes. Phase-contrast and confocal microscopy show that Apoe(-/-) astrocytes do not respond to or internalize Abeta deposits to the same extent as do wild-type astrocytes. Thus, Apoe seems to be important in the degradation and clearance of deposited Abeta species by astrocytes, a process that may be impaired in Alzheimer disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Apolipoproteins E / physiology*
  • Astrocytes / metabolism*
  • Cell Aggregation
  • Cell Survival
  • Cells, Cultured
  • Low Density Lipoprotein Receptor-Related Protein-1 / physiology
  • Mice
  • Mice, Inbred C57BL


  • Amyloid beta-Peptides
  • Apolipoproteins E
  • Low Density Lipoprotein Receptor-Related Protein-1