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@INPROCEEDINGS{Schlachetzki:283066,
author = {Schlachetzki, Johannes C M and Zhou, Yi and Spann, Nathan
and Kleemann, Kilian Leon and McManus, Roisin M and Heneka,
Michael T and Butovsky, Oleg and Glass, Christopher K},
title = {{D}ecoding transcriptional regulation of microglia
associated with amyloid plaques},
journal = {Alzheimer's and dementia},
volume = {21},
number = {Suppl 1},
issn = {1552-5260},
reportid = {DZNE-2025-01473},
pages = {e106751},
year = {2025},
abstract = {Beyond the progressive accumulation of amyloid-beta and
hyperphosphorylated tau, Alzheimer's disease (AD) is
accompanied by phenotypic changes in microglia, the innate
immune cells of the brain. In particular, microglia in the
vicinity of Amyloid-plaques, also known as MGnD or DAM, are
defined by distinct changes in their gene expression
signature, e.g., upregulation of Trem2 mRNA. However, the
precise transcriptional mechanism that drives microglia
phenotype in response to amyloid is not defined.Here, we
isolated microglia from the APP/PS1 transgenic mouse model
followed by ATAC-seq.We provide evidence for a model in
which differential activation of a common set of
transcriptional regulators that includes members of the
MITF/TFE, AP-1 and EGR transcription factor families drives
the amyloid-plaque associated microglia
phenotype.Collectively, these findings reveal the framework
of the transcriptional circuitry that is used to establish a
range of neurodegenerative pathology-associated microglia
phenotypes.},
month = {Jul},
date = {2025-07-27},
organization = {Alzheimer’s Association
International Conference, Toronto
(Canada), 27 Jul 2025 - 31 Jul 2025},
keywords = {Animals / Microglia: metabolism / Microglia: pathology /
Mice, Transgenic / Alzheimer Disease: pathology / Alzheimer
Disease: genetics / Alzheimer Disease: metabolism / Mice /
Disease Models, Animal / Plaque, Amyloid: pathology /
Plaque, Amyloid: metabolism / Brain: pathology / Brain:
metabolism / Amyloid beta-Protein Precursor: genetics /
Humans / Amyloid beta-Peptides: metabolism / Presenilin-1:
genetics / Amyloid beta-Protein Precursor (NLM Chemicals) /
Amyloid beta-Peptides (NLM Chemicals) / Presenilin-1 (NLM
Chemicals)},
cin = {AG McManus},
ddc = {610},
cid = {I:(DE-2719)1013042},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)1 / PUB:(DE-HGF)16},
pubmed = {pmid:41447077},
pmc = {pmc:PMC12739734},
doi = {10.1002/alz70855_106751},
url = {https://pub.dzne.de/record/283066},
}