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000278791 1001_ $$0P:(DE-2719)9000326$$aVillacampa, Nàdia$$b0$$eFirst author
000278791 245__ $$aProliferating Microglia Exhibit Unique Transcriptional and Functional Alterations in Alzheimer's Disease.
000278791 260__ $$aLondon$$bSage Publishing$$c2025
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000278791 520__ $$aProliferation of microglia represents a physiological process, which is accelerated in several neurodegenerative disorders including Alzheimer disease (AD). The effect of such neurodegeneration-associated microglial proliferation on function and disease progression remains unclear. Here, we show that proliferation results in profound alterations of cellular function by providing evidence that newly proliferated microglia show impaired beta-amyloid clearance in vivo. Through sorting of proliferating microglia of APP/PS1 mice and subsequent transcriptome analysis, we define unique proliferation-associated transcriptomic signatures that change with age and beta-amyloid accumulation and are characterized by enrichment of immune system-related pathways. Of note, we identify the DEAD-Box Helicase 3 X-Linked (DDX3X) as a key molecule to modulate microglia activation and cytokine secretion and it is expressed in the AD brain. Together, these results argue for a novel concept by which phenotypic and functional microglial changes occur longitudinally as a response to accelerated proliferation in a neurodegenerative environment.
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000278791 650_7 $$2Other$$aAlzheimer’s disease
000278791 650_7 $$2Other$$ainflammasome
000278791 650_7 $$2Other$$amicroglia
000278791 650_7 $$2Other$$aproliferation
000278791 650_7 $$2Other$$atranscriptome
000278791 650_7 $$2NLM Chemicals$$aAmyloid beta-Protein Precursor
000278791 650_7 $$2NLM Chemicals$$aPresenilin-1
000278791 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000278791 650_7 $$0EC 3.6.4.13$$2NLM Chemicals$$aDEAD-box RNA Helicases
000278791 650_2 $$2MeSH$$aAnimals
000278791 650_2 $$2MeSH$$aMicroglia: metabolism
000278791 650_2 $$2MeSH$$aMicroglia: pathology
000278791 650_2 $$2MeSH$$aMicroglia: physiology
000278791 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000278791 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000278791 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000278791 650_2 $$2MeSH$$aCell Proliferation: physiology
000278791 650_2 $$2MeSH$$aMice, Transgenic
000278791 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: genetics
000278791 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: metabolism
000278791 650_2 $$2MeSH$$aMice
000278791 650_2 $$2MeSH$$aPresenilin-1: genetics
000278791 650_2 $$2MeSH$$aPresenilin-1: metabolism
000278791 650_2 $$2MeSH$$aDisease Models, Animal
000278791 650_2 $$2MeSH$$aBrain: pathology
000278791 650_2 $$2MeSH$$aBrain: metabolism
000278791 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000278791 650_2 $$2MeSH$$aDEAD-box RNA Helicases: metabolism
000278791 650_2 $$2MeSH$$aDEAD-box RNA Helicases: genetics
000278791 650_2 $$2MeSH$$aMice, Inbred C57BL
000278791 650_2 $$2MeSH$$aHumans
000278791 650_2 $$2MeSH$$aMale
000278791 7001_ $$0P:(DE-2719)2811644$$aSarlus, Heela$$b1
000278791 7001_ $$0P:(DE-2719)9002177$$aMartorell, Paula$$b2$$udzne
000278791 7001_ $$00009-0009-6736-2544$$aBhalla, Khushbu$$b3
000278791 7001_ $$0P:(DE-HGF)0$$aGomez-Castro, Sergio$$b4
000278791 7001_ $$0P:(DE-2719)9000382$$aVieira-Saecker, Ana$$b5
000278791 7001_ $$aSlutzkin, Ilya$$b6
000278791 7001_ $$0P:(DE-2719)2812735$$aHändler, Kristian$$b7
000278791 7001_ $$00000-0002-8902-4986$$aVenegas, Carmen$$b8
000278791 7001_ $$0P:(DE-2719)2811671$$aMcManus, Róisín$$b9
000278791 7001_ $$0P:(DE-2719)9000845$$aUlas, Thomas$$b10
000278791 7001_ $$0P:(DE-2719)2812219$$aBeyer, Marc$$b11
000278791 7001_ $$00000-0002-6859-1164$$aSegal, Eran$$b12
000278791 7001_ $$0P:(DE-2719)2000008$$aHeneka, Michael$$b13$$eLast author
000278791 773__ $$0PERI:(DE-600)2485467-0$$a10.1080/17590914.2025.2506406$$gVol. 17, no. 1, p. 2506406$$n1$$p2506406$$tASN NEURO$$v17$$x1759-0914$$y2025
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