Literature DB >> 29889572

Triggering receptor expressed on myeloid cells 2 (TREM2): a potential therapeutic target for Alzheimer disease?

Yuetiva Deming1, Zeran Li1, Bruno A Benitez2, Carlos Cruchaga1,3,4,5.   

Abstract

INTRODUCTION: There are currently no effective therapeutics for Alzheimer disease (AD). Clinical trials targeting amyloid beta thus far have shown very little benefit and only in the earliest stages of disease. These limitations have driven research to identify alternative therapeutic targets, one of the most promising is the triggering receptor expressed on myeloid cells 2 (TREM2). Areas covered: Here, we review the literature to-date and discuss the potentials and pitfalls for targeting TREM2 as a potential therapeutic for AD. We focus on research in animal and cell models for AD and central nervous system injury models which may help in understanding the role of TREM2 in disease. Expert opinion: Studies suggest TREM2 plays a key role in AD pathology; however, results have been conflicting about whether TREM2 is beneficial or harmful. More research is necessary before designing TREM2-targeting therapies. Successful therapeutics will most likely be administered early in disease.

Entities:  

Keywords:  Alzheimer disease; TREM2; cerebrospinal fluid; genetic association; microglia

Mesh:

Substances:

Year:  2018        PMID: 29889572      PMCID: PMC6295143          DOI: 10.1080/14728222.2018.1486823

Source DB:  PubMed          Journal:  Expert Opin Ther Targets        ISSN: 1472-8222            Impact factor:   6.902


  106 in total

1.  Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status.

Authors:  Laura Piccio; Yuetiva Deming; Jorge L Del-Águila; Laura Ghezzi; David M Holtzman; Anne M Fagan; Chiara Fenoglio; Daniela Galimberti; Barbara Borroni; Carlos Cruchaga
Journal:  Acta Neuropathol       Date:  2016-01-11       Impact factor: 17.088

2.  TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease.

Authors:  Tyler K Ulland; Wilbur M Song; Stanley Ching-Cheng Huang; Jason D Ulrich; Alexey Sergushichev; Wandy L Beatty; Alexander A Loboda; Yingyue Zhou; Nigel J Cairns; Amal Kambal; Ekaterina Loginicheva; Susan Gilfillan; Marina Cella; Herbert W Virgin; Emil R Unanue; Yaming Wang; Maxim N Artyomov; David M Holtzman; Marco Colonna
Journal:  Cell       Date:  2017-08-10       Impact factor: 41.582

3.  TREM2 regulates microglial cell activation in response to demyelination in vivo.

Authors:  Claudia Cantoni; Bryan Bollman; Danilo Licastro; Mingqiang Xie; Robert Mikesell; Robert Schmidt; Carla M Yuede; Daniela Galimberti; Gunilla Olivecrona; Robyn S Klein; Anne H Cross; Karel Otero; Laura Piccio
Journal:  Acta Neuropathol       Date:  2015-01-29       Impact factor: 17.088

4.  Polygenic score prediction captures nearly all common genetic risk for Alzheimer's disease.

Authors:  Valentina Escott-Price; Maryam Shoai; Richard Pither; Julie Williams; John Hardy
Journal:  Neurobiol Aging       Date:  2016-08-05       Impact factor: 4.673

5.  Disease-Associated Mutations of TREM2 Alter the Processing of N-Linked Oligosaccharides in the Golgi Apparatus.

Authors:  Ji-Seon Park; In Jung Ji; Hyun Joo An; Min-Ji Kang; Sang-Wook Kang; Dong-Hou Kim; Seung-Yong Yoon
Journal:  Traffic       Date:  2015-02-24       Impact factor: 6.215

6.  Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype.

Authors:  Juha Paloneva; Tuula Manninen; Grant Christman; Karine Hovanes; Jami Mandelin; Rolf Adolfsson; Marino Bianchin; Thomas Bird; Roxana Miranda; Andrea Salmaggi; Lisbeth Tranebjaerg; Yrjö Konttinen; Leena Peltonen
Journal:  Am J Hum Genet       Date:  2002-06-21       Impact factor: 11.025

Review 7.  Human-induced pluripotent stem cells: potential for neurodegenerative diseases.

Authors:  Christopher A Ross; Sergey S Akimov
Journal:  Hum Mol Genet       Date:  2014-05-13       Impact factor: 6.150

8.  Expression and processing analyses of wild type and p.R47H TREM2 variant in Alzheimer's disease brains.

Authors:  Li Ma; Mariet Allen; Nobutaka Sakae; Nilufer Ertekin-Taner; Neill R Graff-Radford; Dennis W Dickson; Steven G Younkin; Daniel Sevlever
Journal:  Mol Neurodegener       Date:  2016-11-25       Impact factor: 14.195

9.  An Alzheimer-associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function.

Authors:  Kai Schlepckow; Gernot Kleinberger; Akio Fukumori; Regina Feederle; Stefan F Lichtenthaler; Harald Steiner; Christian Haass
Journal:  EMBO Mol Med       Date:  2017-10       Impact factor: 12.137

10.  TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy.

Authors:  Cheryl E G Leyns; Jason D Ulrich; Mary B Finn; Floy R Stewart; Lauren J Koscal; Javier Remolina Serrano; Grace O Robinson; Elise Anderson; Marco Colonna; David M Holtzman
Journal:  Proc Natl Acad Sci U S A       Date:  2017-10-09       Impact factor: 11.205

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  9 in total

1.  The MS4A gene cluster is a key modulator of soluble TREM2 and Alzheimer's disease risk.

Authors:  Yuetiva Deming; Fabia Filipello; Francesca Cignarella; Claudia Cantoni; Simon Hsu; Robert Mikesell; Zeran Li; Jorge L Del-Aguila; Umber Dube; Fabiana Geraldo Farias; Joseph Bradley; John Budde; Laura Ibanez; Maria Victoria Fernandez; Kaj Blennow; Henrik Zetterberg; Amanda Heslegrave; Per M Johansson; Johan Svensson; Bengt Nellgård; Alberto Lleo; Daniel Alcolea; Jordi Clarimon; Lorena Rami; José Luis Molinuevo; Marc Suárez-Calvet; Estrella Morenas-Rodríguez; Gernot Kleinberger; Michael Ewers; Oscar Harari; Christian Haass; Thomas J Brett; Bruno A Benitez; Celeste M Karch; Laura Piccio; Carlos Cruchaga
Journal:  Sci Transl Med       Date:  2019-08-14       Impact factor: 17.956

Review 2.  Advances in Genetic and Molecular Understanding of Alzheimer's Disease.

Authors:  Laura Ibanez; Carlos Cruchaga; Maria Victoria Fernández
Journal:  Genes (Basel)       Date:  2021-08-15       Impact factor: 4.096

Review 3.  New Insights into Neuroinflammation Involved in Pathogenic Mechanism of Alzheimer's Disease and Its Potential for Therapeutic Intervention.

Authors:  Tiantian Li; Li Lu; Eloise Pember; Xinuo Li; Bocheng Zhang; Zheying Zhu
Journal:  Cells       Date:  2022-06-14       Impact factor: 7.666

4.  Examination of the Effect of Rare Variants in TREM2, ABI3, and PLCG2 in LOAD Through Multiple Phenotypes.

Authors:  Claudia Olive; Laura Ibanez; Fabiana H Geraldo Farias; Fengxian Wang; John P Budde; Joanne B Norton; Jen Gentsch; John C Morris; Zeran Li; Umber Dube; Jorge Del-Aguila; Kristy Bergmann; Joseph Bradley; Bruno A Benitez; Oscar Harari; Anne Fagan; Beau Ances; Carlos Cruchaga; Maria Victoria Fernandez
Journal:  J Alzheimers Dis       Date:  2020       Impact factor: 4.472

5.  TREM2 brain transcript-specific studies in AD and TREM2 mutation carriers.

Authors:  Jorge L Del-Aguila; Bruno A Benitez; Zeran Li; Umber Dube; Kathie A Mihindukulasuriya; John P Budde; Fabiana H G Farias; Maria Victoria Fernández; Laura Ibanez; Shan Jiang; Richard J Perrin; Nigel J Cairns; John C Morris; Oscar Harari; Carlos Cruchaga
Journal:  Mol Neurodegener       Date:  2019-05-08       Impact factor: 14.195

Review 6.  Targeting Microglia-Synapse Interactions in Alzheimer's Disease.

Authors:  Gaia Piccioni; Dalila Mango; Amira Saidi; Massimo Corbo; Robert Nisticò
Journal:  Int J Mol Sci       Date:  2021-02-26       Impact factor: 5.923

7.  Differential Roles of TREM2+ Microglia in Anterograde and Retrograde Axonal Injury Models.

Authors:  Gemma Manich; Ariadna Regina Gómez-López; Beatriz Almolda; Nàdia Villacampa; Mireia Recasens; Kalpana Shrivastava; Berta González; Bernardo Castellano
Journal:  Front Cell Neurosci       Date:  2020-11-20       Impact factor: 5.505

Review 8.  Role of Microglia and Astrocytes in Alzheimer's Disease: From Neuroinflammation to Ca2+ Homeostasis Dysregulation.

Authors:  Giulia Di Benedetto; Chiara Burgaletto; Carlo Maria Bellanca; Antonio Munafò; Renato Bernardini; Giuseppina Cantarella
Journal:  Cells       Date:  2022-09-01       Impact factor: 7.666

9.  Reduced TREM2 activation in microglia of patients with Alzheimer's disease.

Authors:  Yuumi Okuzono; Hiroyuki Sakuma; Shuuichi Miyakawa; Masataka Ifuku; Jonghun Lee; Debashree Das; Antara Banerjee; Yang Zhao; Koji Yamamoto; Tatsuya Ando; Shuji Sato
Journal:  FEBS Open Bio       Date:  2021-09-28       Impact factor: 2.693

  9 in total

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