TY  - CONF
AU  - Schlachetzki, Johannes C M
AU  - Zhou, Yi
AU  - Spann, Nathan
AU  - Kleemann, Kilian Leon
AU  - McManus, Roisin M
AU  - Heneka, Michael T
AU  - Butovsky, Oleg
AU  - Glass, Christopher K
TI  - Decoding transcriptional regulation of microglia associated with amyloid plaques
JO  - Alzheimer's and dementia
VL  - 21
IS  - Suppl 1
SN  - 1552-5260
M1  - DZNE-2025-01473
SP  - e106751
PY  - 2025
AB  - 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.
T2  - Alzheimer’s Association International Conference
CY  - 27 Jul 2025 - 31 Jul 2025, Toronto (Canada)
Y2  - 27 Jul 2025 - 31 Jul 2025
M2  - Toronto, Canada
KW  - Animals
KW  - Microglia: metabolism
KW  - Microglia: pathology
KW  - Mice, Transgenic
KW  - Alzheimer Disease: pathology
KW  - Alzheimer Disease: genetics
KW  - Alzheimer Disease: metabolism
KW  - Mice
KW  - Disease Models, Animal
KW  - Plaque, Amyloid: pathology
KW  - Plaque, Amyloid: metabolism
KW  - Brain: pathology
KW  - Brain: metabolism
KW  - Amyloid beta-Protein Precursor: genetics
KW  - Humans
KW  - Amyloid beta-Peptides: metabolism
KW  - Presenilin-1: genetics
KW  - Amyloid beta-Protein Precursor (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Presenilin-1 (NLM Chemicals)
LB  - PUB:(DE-HGF)1 ; PUB:(DE-HGF)16
C6  - pmid:41447077
C2  - pmc:PMC12739734
DO  - DOI:10.1002/alz70855_106751
UR  - https://pub.dzne.de/record/283066
ER  -