Journal ArticleDOI
Immune attack: the role of inflammation in Alzheimer disease
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TLDR
As inflammation in AD primarily concerns the innate immune system — unlike in 'typical' neuroinflammatory diseases such as multiple sclerosis and encephalitides — the concept of neuroinflammation in AD may need refinement.Abstract:
The past two decades of research into the pathogenesis of Alzheimer disease (AD) have been driven largely by the amyloid hypothesis; the neuroinflammation that is associated with AD has been assumed to be merely a response to pathophysiological events. However, new data from preclinical and clinical studies have established that immune system-mediated actions in fact contribute to and drive AD pathogenesis. These insights have suggested both novel and well-defined potential therapeutic targets for AD, including microglia and several cytokines. In addition, as inflammation in AD primarily concerns the innate immune system - unlike in 'typical' neuroinflammatory diseases such as multiple sclerosis and encephalitides - the concept of neuroinflammation in AD may need refinement.read more
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Journal ArticleDOI
Neurotoxic reactive astrocytes are induced by activated microglia
Shane A. Liddelow,Kevin A. Guttenplan,Laura E. Clarke,Frederick C. Bennett,Christopher J. Bohlen,Lucas Schirmer,Mariko L. Bennett,Alexandra E. Münch,Won-Suk Chung,Todd C. Peterson,Daniel K. Wilton,Arnaud Frouin,Brooke A. Napier,Nikhil Panicker,Manoj Kumar,Marion S. Buckwalter,David H. Rowitch,Valina L. Dawson,Ted M. Dawson,Beth Stevens,Ben A. Barres +20 more
TL;DR: It is shown that activated microglia induce A1 astrocytes by secreting Il-1α, TNF and C1q, and that these cytokines together are necessary and sufficient to induce A2 astroCytes, which are abundant in various human neurodegenerative diseases.
Journal ArticleDOI
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
Reactive Astrocytes: Production, Function, and Therapeutic Potential
Shane A. Liddelow,Ben A. Barres +1 more
TL;DR: Recent studies that demonstrate that different initiating CNS injuries can elicit at least two types of "reactive" astrocytes with strikingly different properties, one type being helpful and the other harmful are summarized.
Journal ArticleDOI
Microglia in Physiology and Disease
TL;DR: The diversity of microglia phenotypes and their responses in health, aging, and disease are described and treatment options that modulate microglial phenotypes are discussed.
Journal ArticleDOI
Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly
Annamaria Cattaneo,Nadia Cattane,Samantha Galluzzi,Stefania Provasi,Nicola Lopizzo,Cristina Festari,Clarissa Ferrari,Ugo Paolo Guerra,Barbara Paghera,Cristina Muscio,Angelo Bianchetti,Giorgio Dalla Volta,Marinella Turla,Maria Cotelli,Michele Gennuso,Alessandro Prelle,Orazio Zanetti,Giulia Lussignoli,Dario Mirabile,Daniele Bellandi,Simona Gentile,Gloria Belotti,Daniele Villani,Taoufiq Harach,Tristan Bolmont,Alessandro Padovani,Marina Boccardi,Giovanni B. Frisoni +27 more
TL;DR: The data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundances of an anti-inflammatoryTaxon, E. rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis.
References
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Journal ArticleDOI
The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics
John Hardy,Dennis J. Selkoe +1 more
TL;DR: It has been more than 10 years since it was first proposed that the neurodegeneration in Alzheimer's disease (AD) may be caused by deposition of amyloid β-peptide in plaques in brain tissue and the rest of the disease process is proposed to result from an imbalance between Aβ production and Aβ clearance.
Journal Article
Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins.
TL;DR: A panel of antigen-specific mouse helper T cell clones was characterized according to patterns of lymphokine activity production, and two types of T cell were distinguished.
Journal ArticleDOI
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide.
Christian Haass,Dennis J. Selkoe +1 more
TL;DR: Findings in other neurodegenerative diseases indicate that a broadly similar process of neuronal dysfunction is induced by diffusible oligomers of misfolded proteins.
Journal ArticleDOI
Inflammation and Alzheimer's disease.
Haruhiko Akiyama,Steven W. Barger,Scott R. Barnum,B Bradt,Jürgen Bauer,Greg M. Cole,Neil R. Cooper,Piet Eikelenboom,Mark R. Emmerling,Bernd L. Fiebich,Caleb E. Finch,Sally A. Frautschy,W. S. T. Griffin,Harald Hampel,Michael Hüll,Gary E. Landreth,Lih-Fen Lue,Robert E. Mrak,Ian R. A. Mackenzie,Patrick L. McGeer,M K O'Banion,Joel S. Pachter,Giulio Maria Pasinetti,C Plata-Salaman,Joseph G. Rogers,Russell E. Rydel,Yueyang Shen,Wolfgang J. Streit,Ronald Strohmeyer,I Tooyoma,F L van Muiswinkel,R. Veerhuis,David G. Walker,Scott D. Webster,Beatrice Hauss–Wegrzyniak,Gary L. Wenk,Tony Wyss-Coray +36 more
TL;DR: By better understanding AD inflammatory and immunoregulatory processes, it should be possible to develop anti-inflammatory approaches that may not cure AD but will likely help slow the progression or delay the onset of this devastating disorder.
Journal ArticleDOI
Macrophage Activation and Polarization: Nomenclature and Experimental Guidelines
Peter J. Murray,Judith E. Allen,Subhra K. Biswas,Edward A. Fisher,Derek W. Gilroy,Sergij Goerdt,Siamon Gordon,John A. Hamilton,Lionel B. Ivashkiv,Toby Lawrence,Massimo Locati,Alberto Mantovani,Fernando O. Martinez,Jean-Louis Mege,David M. Mosser,Gioacchino Natoli,Jeroen P. J. Saeij,Joachim L. Schultze,Kari Ann Shirey,Antonio Sica,Jill Suttles,Irina A. Udalova,Jo A. Van Ginderachter,Stefanie N. Vogel,Thomas A. Wynn +24 more
TL;DR: A set of standards encompassing three principles-the source of macrophages, definition of the activators, and a consensus collection of markers to describe macrophage activation are described with the goal of unifying experimental standards for diverse experimental scenarios.
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