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

Abstract

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.

• Authors: Milla Koistinaho, Suizhen Lin, Xin Wu, Michail Esterman, Deanna Koger, Jeffrey Hanson, Richard Higgs, Feng Liu, Seema Malkani, Kelly R Bales, Steven M Paul
• Journal: Nature medicine (Nat Med) Vol. 10 Issue 7 Pg. 719-26 (Jul 2004) ISSN: 1078-8956 [Print] United States
• PMID: 15195085 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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