title: The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia.
abstract: BACKGROUND
  The objective of this study was to elucidate the relationship between the triggering receptor expressed on myeloid cells 2 (TREM2) risk variant, neuropathological lesions, alterations in gene and protein expression, and the severity of neuroinflammation.
  
  
  METHODS
  The genetic association study of the R47 H TREM2 variant with Alzheimer's disease (AD), neuropathology, and changes in TREM2 and TYRO protein tyrosine kinase-binding protein (TYROBP) gene and protein expression, and neuroinflammatory markers.
  
  
  RESULTS
  The TREM2 variant is associated with: (i) AD (odds ratio: 4.76; P = .014); (ii) increased density of amyloid plaques and neurofibrillary tangles in multiple brain regions; (iii) increased TREM2 (P = .041) and TYROBP (P = .006) gene expression; (iv) decreased TREM2 protein levels (P = .016); and (v) upregulation of proinflammatory cytokines (regulated on activation, normal T cell expressed and secreted [RANTES] and interferon [IFN] gamma) (P = .003) and nominal downregulation of protective markers (α2-macroglobulin, interleukin 4 or IL-4, and ApoA1) (P = .018).
  
  
  CONCLUSIONS
  These findings link the TREM2 missense mutation with specific molecular abnormalities and increases in neuropathological lesions in the human brain.
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Science and Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center, Bronx, NY, USA.
authors.forename: Panos
authors.initials: P
authors.lastname: Roussos
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Pavel
authors.initials: P
authors.lastname: Katsel
authors.affiliation: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Fam
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Weilun
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Dushyant P
authors.initials: DP
authors.lastname: Purohit
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center, Bronx, NY, USA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: vahram.haroutunian@mssm.edu.
authors.forename: Vahram
authors.initials: V
authors.lastname: Haroutunian
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics*; D020125:Mutation, Missense; D022423:Myeloid Cells; D058225:Plaque, Amyloid / Q000473:pathology; D011971:Receptors, Immunologic / Q000235:genetics*; D012306:Risk
chemical_list: D053327:Apolipoprotein E4; C508598:IL4 protein, human; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C498715:TREM2 protein, human; D015847:Interleukin-4
keywords: Gene expression; Inflammation; Microglia; Mutation; Protein; TYROBP