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000283066 0247_ $$2ISSN$$a1552-5279
000283066 037__ $$aDZNE-2025-01473
000283066 041__ $$aEnglish
000283066 082__ $$a610
000283066 1001_ $$aSchlachetzki, Johannes C M$$b0
000283066 1112_ $$aAlzheimer’s Association International Conference$$cToronto$$d2025-07-27 - 2025-07-31$$gAAIC 25$$wCanada
000283066 245__ $$aDecoding transcriptional regulation of microglia associated with amyloid plaques
000283066 260__ $$c2025
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000283066 520__ $$aBeyond the progressive accumulation of amyloid-beta and hyperphosphorylated tau, Alzheimer's disease (AD) is accompanied by phenotypic changes in microglia, the innate immune cells of the brain. In particular, microglia in the vicinity of Amyloid-plaques, also known as MGnD or DAM, are defined by distinct changes in their gene expression signature, e.g., upregulation of Trem2 mRNA. However, the precise transcriptional mechanism that drives microglia phenotype in response to amyloid is not defined.Here, we isolated microglia from the APP/PS1 transgenic mouse model followed by ATAC-seq.We provide evidence for a model in which differential activation of a common set of transcriptional regulators that includes members of the MITF/TFE, AP-1 and EGR transcription factor families drives the amyloid-plaque associated microglia phenotype.Collectively, these findings reveal the framework of the transcriptional circuitry that is used to establish a range of neurodegenerative pathology-associated microglia phenotypes.
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000283066 650_7 $$2NLM Chemicals$$aAmyloid beta-Protein Precursor
000283066 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000283066 650_7 $$2NLM Chemicals$$aPresenilin-1
000283066 650_2 $$2MeSH$$aAnimals
000283066 650_2 $$2MeSH$$aMicroglia: metabolism
000283066 650_2 $$2MeSH$$aMicroglia: pathology
000283066 650_2 $$2MeSH$$aMice, Transgenic
000283066 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000283066 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000283066 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000283066 650_2 $$2MeSH$$aMice
000283066 650_2 $$2MeSH$$aDisease Models, Animal
000283066 650_2 $$2MeSH$$aPlaque, Amyloid: pathology
000283066 650_2 $$2MeSH$$aPlaque, Amyloid: metabolism
000283066 650_2 $$2MeSH$$aBrain: pathology
000283066 650_2 $$2MeSH$$aBrain: metabolism
000283066 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: genetics
000283066 650_2 $$2MeSH$$aHumans
000283066 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000283066 650_2 $$2MeSH$$aPresenilin-1: genetics
000283066 7001_ $$0P:(DE-HGF)0$$aZhou, Yi$$b1
000283066 7001_ $$aSpann, Nathan$$b2
000283066 7001_ $$aKleemann, Kilian Leon$$b3
000283066 7001_ $$0P:(DE-2719)2811671$$aMcManus, Roisin M$$b4$$udzne
000283066 7001_ $$aHeneka, Michael T$$b5
000283066 7001_ $$aButovsky, Oleg$$b6
000283066 7001_ $$aGlass, Christopher K$$b7
000283066 773__ $$0PERI:(DE-600)2201940-6$$a10.1002/alz70855_106751$$gVol. 21 Suppl 1, no. Suppl 1, p. e106751$$nSuppl 1$$pe106751$$tAlzheimer's and dementia$$v21$$x1552-5260$$y2025
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