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.


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.


CONCLUSIONS
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.
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Yoko
Y
Mori
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Yuta
Y
Yoshino
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Shinichiro
S
Ochi
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Kiyohiro
K
Yamazaki
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Kentaro
K
Kawabe
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Masao
M
Abe
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Tomoji
T
Kitano
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Yuki
Y
Ozaki
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Taku
T
Yoshida
Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho, Tokushima, Japan.
Shusuke
S
Numata
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Takaaki
T
Mori
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Junichi
J
Iga
Kuroda Hospital, Masaki-cho, Ehime, Japan.
Norio
N
Kuroda
Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho, Tokushima, Japan.
Tetsuro
T
Ohmori
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Shu-Ichi
S
Ueno
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008060:Lipodystrophy / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D013344:Subacute Sclerosing Panencephalitis / Q000235:genetics; D015854:Up-Regulation
D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C498715:TREM2 protein, human