Amyloid-beta (Aβ) aggregation plays an important
role in
the development of Alzheimer’s disease (AD). In the AD brain,
amyloid plaques are surrounded by reactive astrocytes, and many essential
functions of astrocytes have been reported to be mediated by protein
secretion. However, the roles of activated astrocytes in AD progression
are under intense debate. To provide an in-depth view of the secretomes
of activated astrocytes, we present in this study a quantitative profile
of rat hippocampal astrocyte secretomes at multiple time points after
both brief and sustained Aβ1–42 stimulation.
Using SILAC labeling and LC–MS/MS analyses, we identified 19
up-regulated secreted proteins after Aβ1–42 treatment. These differentially expressed proteins have been suggested
to be involved in key aspects of biological processes, such as cell
recruitment, Aβ clearance, and regulation of neurogenesis. Particularly,
we validated the role played by CXCL10 in promoting astrocyte aggregation
around amyloid plagues through in vitro cell migration
analysis. This research provides global, quantitative profiling of
astrocyte secretomes produced on Aβ stimulation and hence provides
a detailed molecular basis for the relationship between amyloid plaques
and astrocyte aggregation; the findings thus have important implications
for further investigations into AD development and therapy.