publication . Article . Other literature type . 2015

TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models

Taylor R. Jay; Crystal M. Miller; Paul J. Cheng; Leah C. Graham; Shane Bemiller; Margaret L. Broihier; Guixiang Xu; Daniel Margevicius; J. Colleen Karlo; Gregory L. Sousa; ...
Open Access English
  • Published: 02 Mar 2015 Journal: The Journal of Experimental Medicine, volume 212, issue 3, pages 287-295 (issn: 0022-1007, eissn: 1540-9538, Copyright policy)
  • Publisher: The Rockefeller University Press
Abstract
Jay and colleagues show that TREM2 deficiency reduces the number of macrophages infiltrating the brain and is protective against disease pathogenesis in mouse models of Alzheimer’s disease.
Subjects
free text keywords: Brief Definitive Report, Immunology, Immunology and Allergy, Neurodegeneration, medicine.disease, medicine, Alzheimer's disease, Microglia, medicine.anatomical_structure, Cell type, TREM2, Inflammation, medicine.symptom, business.industry, business, Pathology, medicine.medical_specialty, Pathogenesis, Amyloid
Funded by
NIH| Medical Scientist Training Program
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5T32GM007250-41
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
,
NIH| Modifiers of beta-amyloid metabolism and deposition
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01AG023012-09
  • Funding stream: NATIONAL INSTITUTE ON AGING
,
NIH| Predoctoral Training in Neurosciences
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5T32NS067431-14
  • Funding stream: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
32 references, page 1 of 3

Akiyama H., Barger S., Barnum S., Bradt B., Bauer J., Cole G.M., Cooper N.R., Eikelenboom P., Emmerling M., Fiebich B.L., 2000 Inflammation and Alzheimer’s disease. Neurobiol. Aging.21:383–421 10.1016/S0197-4580(00)00124-X 10858586 [OpenAIRE] [PubMed] [DOI]

Bird T.D., Koerker R.M., Leaird B.J., Vlcek B.W., and Thorning D.R.1983 Lipomembranous polycystic osteodysplasia (brain, bone, and fat disease): a genetic cause of presenile dementia. Neurology.33:81–86 10.1212/WNL.33.1.81 6681564 [OpenAIRE] [PubMed] [DOI]

Borroni B., Ferrari F., Galimberti D., Nacmias B., Barone C., Bagnoli S., Fenoglio C., Piaceri I., Archetti S., Bonvicini C., 2014 Heterozygous TREM2 mutations in frontotemporal dementia. Neurobiol. Aging.35:934.e7–934.e10 10.1016/j.neurobiolaging.2013.09.017 24139279 [OpenAIRE] [PubMed] [DOI]

Butovsky O., Jedrychowski M.P., Moore C.S., Cialic R., Lanser A.J., Gabriely G., Koeglsperger T., Dake B., Wu P.M., Doykan C.E., 2014 Identification of a unique TGF-β–dependent molecular and functional signature in microglia. Nat. Neurosci.17:131–143 10.1038/nn.3599 24316888 [OpenAIRE] [PubMed] [DOI]

Cady J., Koval E.D., Benitez B.A., Zaidman C., Jockel-Balsarotti J., Allred P., Baloh R.H., Ravits J., Simpson E., Appel S.H., 2014 TREM2 variant p.R47H as a risk factor for sporadic amyotrophic lateral sclerosis. JAMA Neurol.71:449–453 10.1001/jamaneurol.2013.6237 24535663 [OpenAIRE] [PubMed] [DOI]

Chiu I.M., Morimoto E.T., Goodarzi H., Liao J.T., O’Keeffe S., Phatnani H.P., Muratet M., Carroll M.C., Levy S., Tavazoie S., 2013 A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model. Cell Reports.4:385–401 10.1016/j.celrep.2013.06.018 23850290 [OpenAIRE] [PubMed] [DOI]

Colonna M.2003 TREMs in the immune system and beyond. Nat. Rev. Immunol.3:445–453 10.1038/nri1106 12776204 [OpenAIRE] [PubMed] [DOI]

Cramer P.E., Cirrito J.R., Wesson D.W., Lee C.Y., Karlo J.C., Zinn A.E., Casali B.T., Restivo J.L., Goebel W.D., Ja mes M.J., 2012 ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models. Science.335:1503–1506 10.1126/science.1217697 22323736 [OpenAIRE] [PubMed] [DOI]

Forabosco P., Ramasamy A., Trabzuni D., Walker R., Smith C., Bras J., Levine A.P., Hardy J., Pocock J.M., Guerreiro R., 2013 Insights into TREM2 biology by network analysis of human brain gene expression data. Neurobiol. Aging.34:2699–2714 10.1016/j.neurobiolaging.2013.05.001 23855984 [OpenAIRE] [PubMed] [DOI]

Frank S., Burbach G.J., Bonin M., Walter M., Streit W., Bechmann I., and Deller T.2008 TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice. Glia.56:1438–1447 10.1002/glia.20710 18551625 [OpenAIRE] [PubMed] [DOI]

Guerreiro R., Wojtas A., Bras J., Carrasquillo M., Rogaeva E., Majounie E., Cruchaga C., Sassi C., Kauwe J.S., Younkin S., Alzheimer Genetic Analysis Group. 2013 TREM2 variants in Alzheimer’s disease. N. Engl. J. Med.368:117–127 10.1056/NEJMoa1211851 23150934 [OpenAIRE] [PubMed] [DOI]

Guerreiro R.J., Lohmann E., Brás J.M., Gibbs J.R., Rohrer J.D., Gurunlian N., Dursun B., Bilgic B., Hanagasi H., Gurvit H., 2013 Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement. JAMA Neurol.70:78–84 10.1001/jamaneurol.2013.579 23318515 [OpenAIRE] [PubMed] [DOI]

Hickman S.E., Kingery N.D., Ohsumi T.K., Borowsky M.L., Wang L.C., Means T.K., and El Khoury J.2013 The microglial sensome revealed by direct RNA sequencing. Nat. Neurosci.16:1896–1905 10.1038/nn.3554 24162652 [OpenAIRE] [PubMed] [DOI]

Jiang T., Tan L., Zhu X.C., Zhang Q.Q., Cao L., Tan M.S., Gu L.Z., Wang H.F., Ding Z.Z., Zhang Y.D., and Yu J.T.2014 Upregulation of TREM2 ameliorates neuropathology and rescues spatial cognitive impairment in a transgenic mouse model of Alzheimer’s disease. Neuropsychopharmacology.39:2949–2962 10.1038/npp.2014.164 25047746 [OpenAIRE] [PubMed] [DOI]

Jonsson T., Stefansson H., Steinberg S., Jonsdottir I., Jonsson P.V., Snaedal J., Bjornsson S., Huttenlocher J., Levey A.I., Lah J.J., 2013 Variant of TREM2 associated with the risk of Alzheimer’s disease. N. Engl. J. Med.368:107–116 10.1056/NEJMoa1211103 23150908 [OpenAIRE] [PubMed] [DOI]

32 references, page 1 of 3
Abstract
Jay and colleagues show that TREM2 deficiency reduces the number of macrophages infiltrating the brain and is protective against disease pathogenesis in mouse models of Alzheimer’s disease.
Subjects
free text keywords: Brief Definitive Report, Immunology, Immunology and Allergy, Neurodegeneration, medicine.disease, medicine, Alzheimer's disease, Microglia, medicine.anatomical_structure, Cell type, TREM2, Inflammation, medicine.symptom, business.industry, business, Pathology, medicine.medical_specialty, Pathogenesis, Amyloid
Funded by
NIH| Medical Scientist Training Program
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5T32GM007250-41
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
,
NIH| Modifiers of beta-amyloid metabolism and deposition
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01AG023012-09
  • Funding stream: NATIONAL INSTITUTE ON AGING
,
NIH| Predoctoral Training in Neurosciences
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5T32NS067431-14
  • Funding stream: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
32 references, page 1 of 3

Akiyama H., Barger S., Barnum S., Bradt B., Bauer J., Cole G.M., Cooper N.R., Eikelenboom P., Emmerling M., Fiebich B.L., 2000 Inflammation and Alzheimer’s disease. Neurobiol. Aging.21:383–421 10.1016/S0197-4580(00)00124-X 10858586 [OpenAIRE] [PubMed] [DOI]

Bird T.D., Koerker R.M., Leaird B.J., Vlcek B.W., and Thorning D.R.1983 Lipomembranous polycystic osteodysplasia (brain, bone, and fat disease): a genetic cause of presenile dementia. Neurology.33:81–86 10.1212/WNL.33.1.81 6681564 [OpenAIRE] [PubMed] [DOI]

Borroni B., Ferrari F., Galimberti D., Nacmias B., Barone C., Bagnoli S., Fenoglio C., Piaceri I., Archetti S., Bonvicini C., 2014 Heterozygous TREM2 mutations in frontotemporal dementia. Neurobiol. Aging.35:934.e7–934.e10 10.1016/j.neurobiolaging.2013.09.017 24139279 [OpenAIRE] [PubMed] [DOI]

Butovsky O., Jedrychowski M.P., Moore C.S., Cialic R., Lanser A.J., Gabriely G., Koeglsperger T., Dake B., Wu P.M., Doykan C.E., 2014 Identification of a unique TGF-β–dependent molecular and functional signature in microglia. Nat. Neurosci.17:131–143 10.1038/nn.3599 24316888 [OpenAIRE] [PubMed] [DOI]

Cady J., Koval E.D., Benitez B.A., Zaidman C., Jockel-Balsarotti J., Allred P., Baloh R.H., Ravits J., Simpson E., Appel S.H., 2014 TREM2 variant p.R47H as a risk factor for sporadic amyotrophic lateral sclerosis. JAMA Neurol.71:449–453 10.1001/jamaneurol.2013.6237 24535663 [OpenAIRE] [PubMed] [DOI]

Chiu I.M., Morimoto E.T., Goodarzi H., Liao J.T., O’Keeffe S., Phatnani H.P., Muratet M., Carroll M.C., Levy S., Tavazoie S., 2013 A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model. Cell Reports.4:385–401 10.1016/j.celrep.2013.06.018 23850290 [OpenAIRE] [PubMed] [DOI]

Colonna M.2003 TREMs in the immune system and beyond. Nat. Rev. Immunol.3:445–453 10.1038/nri1106 12776204 [OpenAIRE] [PubMed] [DOI]

Cramer P.E., Cirrito J.R., Wesson D.W., Lee C.Y., Karlo J.C., Zinn A.E., Casali B.T., Restivo J.L., Goebel W.D., Ja mes M.J., 2012 ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models. Science.335:1503–1506 10.1126/science.1217697 22323736 [OpenAIRE] [PubMed] [DOI]

Forabosco P., Ramasamy A., Trabzuni D., Walker R., Smith C., Bras J., Levine A.P., Hardy J., Pocock J.M., Guerreiro R., 2013 Insights into TREM2 biology by network analysis of human brain gene expression data. Neurobiol. Aging.34:2699–2714 10.1016/j.neurobiolaging.2013.05.001 23855984 [OpenAIRE] [PubMed] [DOI]

Frank S., Burbach G.J., Bonin M., Walter M., Streit W., Bechmann I., and Deller T.2008 TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice. Glia.56:1438–1447 10.1002/glia.20710 18551625 [OpenAIRE] [PubMed] [DOI]

Guerreiro R., Wojtas A., Bras J., Carrasquillo M., Rogaeva E., Majounie E., Cruchaga C., Sassi C., Kauwe J.S., Younkin S., Alzheimer Genetic Analysis Group. 2013 TREM2 variants in Alzheimer’s disease. N. Engl. J. Med.368:117–127 10.1056/NEJMoa1211851 23150934 [OpenAIRE] [PubMed] [DOI]

Guerreiro R.J., Lohmann E., Brás J.M., Gibbs J.R., Rohrer J.D., Gurunlian N., Dursun B., Bilgic B., Hanagasi H., Gurvit H., 2013 Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement. JAMA Neurol.70:78–84 10.1001/jamaneurol.2013.579 23318515 [OpenAIRE] [PubMed] [DOI]

Hickman S.E., Kingery N.D., Ohsumi T.K., Borowsky M.L., Wang L.C., Means T.K., and El Khoury J.2013 The microglial sensome revealed by direct RNA sequencing. Nat. Neurosci.16:1896–1905 10.1038/nn.3554 24162652 [OpenAIRE] [PubMed] [DOI]

Jiang T., Tan L., Zhu X.C., Zhang Q.Q., Cao L., Tan M.S., Gu L.Z., Wang H.F., Ding Z.Z., Zhang Y.D., and Yu J.T.2014 Upregulation of TREM2 ameliorates neuropathology and rescues spatial cognitive impairment in a transgenic mouse model of Alzheimer’s disease. Neuropsychopharmacology.39:2949–2962 10.1038/npp.2014.164 25047746 [OpenAIRE] [PubMed] [DOI]

Jonsson T., Stefansson H., Steinberg S., Jonsdottir I., Jonsson P.V., Snaedal J., Bjornsson S., Huttenlocher J., Levey A.I., Lah J.J., 2013 Variant of TREM2 associated with the risk of Alzheimer’s disease. N. Engl. J. Med.368:107–116 10.1056/NEJMoa1211103 23150908 [OpenAIRE] [PubMed] [DOI]

32 references, page 1 of 3
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