|Title||Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-beta peptides.|
|Publication Type||Journal Article|
|Year of Publication||2004|
|Authors||Koistinaho M, Lin S, Wu X, Esterman M, Koger D, Hanson J, Higgs R, Liu F, Malkani S, Bales KR, Paul SM|
|Date Published||2004 Jul|
|Keywords||Amyloid beta-Peptides, Animals, Apolipoproteins E, Astrocytes, Cell Aggregation, Cell Survival, Cells, Cultured, Low Density Lipoprotein Receptor-Related Protein-1, Mice, Mice, Inbred C57BL|
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.
|Alternate Journal||Nat. Med.|