TREM2 upregulation correlates with 5-hydroxymethycytosine enrichment in Alzheimer's disease hippocampus

TREM2 上调与阿尔茨海默病海马中 5-羟甲基胞嘧啶富集相关

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作者:Naiara Celarain, Javier Sánchez-Ruiz de Gordoa, María Victoria Zelaya, Miren Roldán, Rosa Larumbe, Laura Pulido, Carmen Echavarri, Maite Mendioroz

Background

Recent genome-wide association studies revealed TREM2 rs75932628-T variant to be associated with Alzheimer's disease (AD) and other neurodegenerative diseases. However, the role that TREM2 plays in sporadic AD is largely unknown. Our

Conclusions

TREM2 mRNA levels are increased in the human hippocampus in AD cases compared to controls. DNA methylation, and particularly 5hmC, may be involved in regulating TREM2 mRNA expression in the AD brain. Further studies are guaranteed to investigate in depth the role of 5hmC in AD and other neurodegenerative disorders.

Results

A 3.4-fold increase in TREM2 mRNA levels was observed in the hippocampus of AD cases compared to controls (p = 1.1E-05). Interestingly, TREM2 methylation was higher in AD cases compared to controls (76.2 % ± 15.5 versus 57.9 % ± 17.1; p = 0.0016). Moreover, TREM2 mRNA levels in the AD hippocampus correlated with enrichment in 5hmC at the TREM2 gene body (r = 0.771; p = 0.005). Conclusions: TREM2 mRNA levels are increased in the human hippocampus in AD cases compared to controls. DNA methylation, and particularly 5hmC, may be involved in regulating TREM2 mRNA expression in the AD brain. Further studies are guaranteed to investigate in depth the role of 5hmC in AD and other neurodegenerative disorders.

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