Journal ArticleDOI
TREM2 variants: new keys to decipher Alzheimer disease pathogenesis
Marco Colonna,Yaming Wang +1 more
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TLDR
How TREM2 may control the microglia response to Aβ and its impact on microglial senescence is discussed, as well as the interaction of TREM 2 with other molecules that are encoded by gene variants associated with AD and the hypothetical consequences of the cleavage of T REM2 from the cell surface.Abstract:
Genome-wide association studies have identified rare variants of the gene that encodes triggering receptor expressed on myeloid cells 2 (TREM2) - an immune receptor that is found in brain microglia - as risk factors for non-familial Alzheimer disease (AD). Furthermore, animal studies have indicated that microglia have an important role in the brain response to amyloid-β (Aβ) plaques and that TREM2 variants may have an impact on such a function. We discuss how TREM2 may control the microglial response to Aβ and its impact on microglial senescence, as well as the interaction of TREM2 with other molecules that are encoded by gene variants associated with AD and the hypothetical consequences of the cleavage of TREM2 from the cell surface.read more
Citations
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A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Hadas Keren-Shaul,Amit Spinrad,Assaf Weiner,Assaf Weiner,Orit Matcovitch-Natan,Raz Dvir-Szternfeld,Tyler K. Ulland,Eyal David,Kuti Baruch,David Lara-Astaiso,Beáta Tóth,Shalev Itzkovitz,Marco Colonna,Michal Schwartz,Ido Amit +14 more
TL;DR: A novel microglia type associated with neurodegenerative diseases (DAM) is described and it is revealed that the DAM program is activated in a two-step process that involves downregulation of microglian checkpoints, followed by activation of a Trem2-dependent program.
Journal ArticleDOI
Microglia Function in the Central Nervous System During Health and Neurodegeneration.
Marco Colonna,Oleg Butovsky +1 more
TL;DR: The complexity of targeting microglia for therapeutic intervention in neurodegenerative diseases is highlighted and the spectrum of microglial phenotypes during development, homeostasis, and disease is characterized.
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Microglia emerge as central players in brain disease.
Michael W. Salter,Beth Stevens +1 more
TL;DR: Recent developments in the rapidly expanding understanding of the function, as well as the dysfunction, of microglia in disorders of the CNS are focused on.
Journal ArticleDOI
Microglia and macrophages in brain homeostasis and disease
Qingyun Li,Ben A. Barres +1 more
TL;DR: The current knowledge of how and where brain macrophages are generated is reviewed, with a focus on parenchymal microglia and their normal functions during development and homeostasis are discussed.
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Neuronal Cell Death.
TL;DR: Which forms of cell death occur in stroke and Alzheimer's disease are reassess, and why it has been so difficult to pinpoint the type of neuronal death involved is discussed.
References
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TL;DR: The APOE-epsilon 4 allele is associated with the common late onset familial and sporadic forms of Alzheimer9s disease (AD) in 42 families with late onset AD.
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Warren J. Strittmatter,Ann M. Saunders,Donald E. Schmechel,Margaret A. Pericak-Vance,Jan J. Enghild,Guy S. Salvesen,Allen D. Roses +6 more
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An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex
Ye Zhang,Kenian Chen,Steven A. Sloan,Mariko L. Bennett,Anja R. Scholze,Sean O'Keeffe,Hemali Phatnani,Paolo Guarnieri,Christine Caneda,Nadine Ruderisch,Shuyun Deng,Shane A. Liddelow,Chaolin Zhang,Richard Daneman,Tom Maniatis,Ben A. Barres,Jian Qian Wu +16 more
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Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease
Denise Harold,Richard Abraham,Paul Hollingworth,Rebecca Sims,Amy Gerrish,Marian L. Hamshere,Jaspreet Singh Pahwa,Valentina Moskvina,Kimberley Dowzell,Amy L. Williams,Nicola L. Jones,Charlene Thomas,Alexandra Stretton,Angharad R. Morgan,Simon Lovestone,John Powell,Petroula Proitsi,Michelle K. Lupton,Carol Brayne,David C. Rubinsztein,Michael Gill,Brian A. Lawlor,Aoibhinn Lynch,Kevin Morgan,Kristelle Brown,Peter Passmore,David Craig,Bernadette McGuinness,Stephen Todd,Clive Holmes,David M. A. Mann,A. David Smith,Seth Love,Patrick G. Kehoe,John Hardy,Simon Mead,Nick C. Fox,Martin N. Rossor,John Collinge,Wolfgang Maier,Frank Jessen,Britta Schürmann,Hendrik van den Bussche,Isabella Heuser,Johannes Kornhuber,Jens Wiltfang,Martin Dichgans,Lutz Frölich,Harald Hampel,Harald Hampel,Michael Hüll,Dan Rujescu,Alison Goate,John S. K. Kauwe,Carlos Cruchaga,Petra Nowotny,John C. Morris,Kevin Mayo,Kristel Sleegers,Karolien Bettens,Sebastiaan Engelborghs,Peter Paul De Deyn,Christine Van Broeckhoven,Gill Livingston,Nicholas Bass,Hugh Gurling,Andrew McQuillin,Rhian Gwilliam,Panagiotis Deloukas,Ammar Al-Chalabi,Christopher Shaw,Magda Tsolaki,Andrew B. Singleton,Rita Guerreiro,Thomas W. Mühleisen,Markus M. Nöthen,Susanne Moebus,Karl-Heinz Jöckel,Norman Klopp,H-Erich Wichmann,Minerva M. Carrasquillo,V. Shane Pankratz,Steven G. Younkin,Peter Holmans,Michael Conlon O'Donovan,Michael John Owen,Julie Williams +86 more
TL;DR: A two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals, the most powerful AD GWAS to date, produced compelling evidence for association with Alzheimer's Disease in the combined dataset.
Journal ArticleDOI
TREM2 Variants in Alzheimer's Disease
Rita Guerreiro,Rita Guerreiro,Aleksandra Wojtas,Jose Bras,Minerva M. Carrasquillo,Ekaterina Rogaeva,Elisa Majounie,Carlos Cruchaga,Celeste Sassi,Celeste Sassi,John S. K. Kauwe,Steven G. Younkin,Lili-Naz Hazrati,John Collinge,Jennifer M. Pocock,Tammaryn Lashley,Julie Williams,Jean-Charles Lambert,Philippe Amouyel,Alison Goate,Rosa Rademakers,Kevin Morgan,John Powell,Peter St George-Hyslop,Peter St George-Hyslop,Andrew B. Singleton,John Hardy +26 more
TL;DR: Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease.
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