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

Milla Koistinaho, Suizhen Lin, Xin Wu, Michail Esterman, Deanna Koger, Jeffrey Hanson, Richard Higgs, Feng Liu, Seema Malkani, Kelly R. Bales, Steven M. Paul

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408 Scopus citations

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-β peptides (Aβ) in a mouse model of Alzheimer disease. Given the capacity of astrocytes to degrade Aβ, 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 Aβ present in Aβ plaque-bearing brain sections in vitro. Coincubation with antibodies to either Apoe or Aβ, or with RAP, an antagonist of the low-density lipoprotein receptor family, effectively blocks Aβ degradation by astrocytes. Phase-contrast and confocal microscopy show that Apoe-/- astrocytes do not respond to or internalize Aβ deposits to the same extent as do wild-type astrocytes. Thus, Apoe seems to be important in the degradation and clearance of deposited Aβ species by astrocytes, a process that may be impaired in Alzheimer disease.

Original languageEnglish
Pages (from-to)719-726
Number of pages8
JournalNature medicine
Volume10
Issue number7
DOIs
StatePublished - Jul 1 2004
Externally publishedYes

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    Koistinaho, M., Lin, S., Wu, X., Esterman, M., Koger, D., Hanson, J., Higgs, R., Liu, F., Malkani, S., Bales, K. R., & Paul, S. M. (2004). Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-β peptides. Nature medicine, 10(7), 719-726. https://doi.org/10.1038/nm1058