TREM2 mRNA Expression in Leukocytes Is Increased in Alzheimer's Disease and Schizophrenia

PLoS One. 2015 Sep 2;10(9):e0136835. doi: 10.1371/journal.pone.0136835. eCollection 2015.

Abstract

TREM2 and TYROBP are causal genes for Nasu-Hakola disease (NHD), a rare autosomal recessive disease characterized by bone lesions and early-onset progressive dementia. TREM2 forms a receptor signaling complex with TYROBP, which triggers the activation of immune responses in macrophages and dendritic cells, and the functional polymorphism of TREM2 is reported to be associated with neurodegenerative disorders such as Alzheimer's disease (AD). The objective of this study was to reveal the involvement of TYROBP and TREM2 in the pathophysiology of AD and schizophrenia.

Methods: We investigated the mRNA expression level of the 2 genes in leukocytes of 26 patients with AD and 24 with schizophrenia in comparison with age-matched controls. Moreover, we performed gene association analysis between these 2 genes and schizophrenia.

Results: No differences were found in TYROBP mRNA expression in patients with AD and schizophrenia; however, TREM2 mRNA expression was increased in patients with AD and schizophrenia compared with controls (P < 0.001). There were no genetic associations of either gene with schizophrenia in Japanese patients.

Conclusion: TREM2 expression in leukocytes is elevated not only in AD but also in schizophrenia. Inflammatory processes involving TREM2 may occur in schizophrenia, as observed in neurocognitive disorders such as AD. TREM2 expression in leukocytes may be a novel biomarker for neurological and psychiatric disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics*
  • Female
  • Humans
  • Leukocytes / metabolism*
  • Lipodystrophy / genetics
  • Male
  • Membrane Glycoproteins / genetics*
  • Osteochondrodysplasias / genetics
  • Polymorphism, Single Nucleotide
  • RNA, Messenger / genetics*
  • Receptors, Immunologic / genetics*
  • Schizophrenia / genetics*
  • Subacute Sclerosing Panencephalitis / genetics
  • Up-Regulation*

Substances

  • Membrane Glycoproteins
  • RNA, Messenger
  • Receptors, Immunologic
  • TREM2 protein, human

Supplementary concepts

  • Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy

Grants and funding

This work was partially supported by a Health and Labor Science Research Grant from the Japanese Ministry of Health, Labour and Welfare; a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology; and the Ehime Graduate University of Medicine’s Good Practice Fund.