Correlation between Hypomethylation of HMOX1 and Cognitive Decline in Patients with Alzheimer’s Disease (abstract only)  

Oleh:

Sung, Hye Youn ; Choi, Eun Nam ; Ahn, Jung-Hyuck

Jenis: Article from Proceeding
Dalam koleksi: The International Symposium on Social Sciences (TISSS) and Hong Kong International Conference on Education, Psychology and Society (HKICEPS) at Hongkong, December 2013, page 899.
Topik: Alzheimer’s disease; Amyloid Precursor Protein; Swedish mutation; DNA methylation; Heme oxygenase-1
Fulltext: Hong Kong-Conference 144.pdf (284.08KB)

Isi artikel

The Swedish mutation of amyloid precursor protein (APP-sw) is one of the mutations leading to familial Alzheimer’s disease (AD) and characterized by excess amyloid beta production and an early-onset of AD. Aberrant DNA methylation status has been reported to be associated with AD pathogenesis, but the underlying molecular mechanism of APP-swmediated epigenetic alterations in AD pathogenesis remains largely unknown. Heme oxidenase-1 (HMOX1) is the enzyme mediating the degradation of heme to ferrous iron, carbon monoxide and biliverdin/bilirubin with its expression up-regulated in neurons and astrocytes of the cerebral cortex and hippocampus in the brain of AD and mild cognitive impairment. Herein, we performed integrated analysis between CpG methylation and mRNA expression and our results revealed that profoundly increased level of HMOX1 expression and the hypomethylation of HMOX1 at the specific promoter CpG site in APP-sw neuroglioma cells. Treatment with the demethylating agent 5-Aza-2'-deoxycytidine restored mRNA expression of HMOX1, implying methylation-dependent transcriptional regulation. We also determined the DNA methylation status at specific promoter CpG site of HMOX1 in the blood of dementia patients. In dementia patients aged 70 and older, the status of DNA hypomethylation was markedly correlated with MMSE (mini mental state examination) score. In this study, we suggest that the methylation status of HMOX1 at specific promoter CpG site may provide a potential molecular biomarker for progression of AD.

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