Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-beta peptides.
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.
Koistinaho
Milla
M
Neuroscience Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
Lin
Suizhen
S
Wu
Xin
X
Esterman
Michail
M
Koger
Deanna
D
Hanson
Jeffrey
J
Higgs
Richard
R
Liu
Feng
F
Malkani
Seema
S
Bales
Kelly R
KR
Paul
Steven M
SM
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology*; D001253:Astrocytes / Q000378:metabolism*; D002449:Cell Aggregation; D002470:Cell Survival; D002478:Cells, Cultured; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D026503:Low Density Lipoprotein Receptor-Related Protein-1