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@MISC{Mller:194998,
author = {Müller, Stephan A and Lichtenthaler, Stefan F},
title = {{D}ataset: {B}eneficial effect of {ACI}-24 vaccination on
microglial phenotypes in an amyloidosis mouse model},
publisher = {PRoteomics IDEntifications Database},
reportid = {DZNE-2023-00181},
year = {2023},
abstract = {Amyloid-beta (Aβ) deposition is an initiating factor in
Alzheimer´s disease (AD). Microglia are the brain immune
cells that surround and phagocytose Aβ, but their
phagocytic capacity declines in AD. This is in agreement
with studies that associate AD risk loci with genes
regulating phagocytic function. Immunotherapies are
currently pursued as therapeutic strategies against AD and
there are increased efforts to understand the role of the
immune system in ameliorating AD pathology. Here, we
evaluated the effect of the Aβ targeting ACI-24 vaccine in
preventing the AD pathology in an amyloidosis mouse model.
ACI-24 vaccination elicited a robust and sustained antibody
response in APPPS1 mice with an accompanying reduction of
Aβ plaque load, amyloid plaque-associated ApoE and
dystrophic neurites as compared to non-vaccinated controls.
Furthermore, plaque-associated microglia had the tendency to
be more activated post vaccination. The lower Aβ plaque
load triggered by vaccination with ACI-24 was in concordance
with the bulk transcriptomic analysis that revealed a
reduction in the expression of several disease-associated
microglial signatures. Accordingly, plaque-distant microglia
displayed a more ramified morphology, supporting beneficial
effects of the vaccination on bulk microglial phenotypes.
Our study demonstrates that administration of the Aβ
targeting vaccine, ACI-24, triggers protective microglial
responses that translate into a reduction of AD pathology
suggesting its use as a safe and cost effective AD
therapeutic intervention.},
cin = {AG Lichtenthaler},
cid = {I:(DE-2719)1110006},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)32},
url = {https://pub.dzne.de/record/194998},
}