Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-beta peptides
| Autor: | Steven M. Paul, Michail A. Esterman, Jeffrey C. Hanson, Xin Wu, Kelly R. Bales, Seema Malkani, Milla Koistinaho, Suizhen Lin, Feng Liu, Richard E. Higgs, Deanna Koger |
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| Rok vydání: | 2004 |
| Předmět: |
Apolipoprotein E
Pathology medicine.medical_specialty Amyloid Amyloid beta Cell Survival Biology General Biochemistry Genetics and Molecular Biology Mice Apolipoproteins E mental disorders medicine Animals Cells Cultured Cell Aggregation Amyloid beta-Peptides Colocalization General Medicine medicine.disease Cell aggregation nervous system diseases Cell biology Mice Inbred C57BL medicine.anatomical_structure Astrocytes biology.protein lipids (amino acids peptides and proteins) Alzheimer's disease Low Density Lipoprotein Receptor-Related Protein-1 Astrocyte Lipoprotein |
| Zdroj: | Nature medicine. 10(7) |
| ISSN: | 1078-8956 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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