The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia

Panos Roussos, Pavel Katsel, Peter Fam, Weilun Tan, Dushyant P. Purohit, Vahram Haroutunian

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Introduction 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). Discussion These findings link the TREM2 missense mutation with specific molecular abnormalities and increases in neuropathological lesions in the human brain.

Original languageEnglish
Pages (from-to)1163-1170
Number of pages8
JournalAlzheimer's and Dementia
Volume11
Issue number10
DOIs
StatePublished - Oct 2015

Keywords

  • Gene expression
  • Inflammation
  • Microglia
  • Mutation
  • Protein
  • TYROBP

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