TREM2 Expression in Schizophrenia

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

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

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.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.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.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

Genotyping results of the selected two tagging SNPs in <i>TYROBP</i> and one tagging SNP in <i>TREM2</i>.

<p>d, minor allele; HWE, Hardy‐Weinberg equilibrium; MAF, Minor Allele Frequency</p><p>The single marker p-value is calculated by Chi-squared test with omission the missing values.</p><p>Genotyping results of the selected two tagging SNPs in <i>TYROBP</i> and one tagging SNP in <i>TREM2</i>.</p

Result of association study in the TYROBP gene.

<p><i>P</i>-value is calculated by Chi-squared test with omission the missing values.</p><p>Result of association study in the TYROBP gene.</p

Characteristics of APOE ɛ4 positive and negative group in AD.

<p>AD, Alzheimer’s Disease; MMSE, Mini Mental State Examination; CDR, Clinical Dementia Rating. The score of 0–3 shows classification of dementia (0 = none, 0.5 = questionable, 1 = mild, 2 = moderate, 3 = severe). The <i>P</i>-value was calculated by Student <i>t</i> test, Chi-squired test, and Fisher’s exact test.</p><p>Characteristics of APOE ɛ4 positive and negative group in AD.</p

Expression of TYOBP (2A) and TREM2 (2B) in APOE ɛ4-positive AD [ɛ4(+) AD], APOE ɛ4-negative AD [ɛ4(−) AD], and AD-cnt groups.

<p>TYROBP expression showed no difference. TREM2 expression was significantly higher in ɛ4-positive AD group than in AD-cnt (including 2 ɛ4-positive subjects) group. The expression levels tended to decline in the following order: ɛ4(+) AD, ɛ4(−) AD, and AD-cnt. <i>P</i> < 0.001 after Bonferroni correction is indicated by * * when the <i>P</i> values were calculated by Mann–Whitney U-test.</p

Characteristics of the selected two tagging SNPs in <i>TYROBP</i> and one tagging SNP in <i>TREM2</i>.

<p>Characteristics of the selected two tagging SNPs in <i>TYROBP</i> and one tagging SNP in <i>TREM2</i>.</p