The Role of Methylated Circulating Nucleic Acids as a Potential Biomarker in Alzheimer’s Disease

Previous studies report detection of high concentrations of circulating nucleic acids (CNAs), which are likely related to cell apoptosis, in the plasma of patients with cancers, stroke, trauma, and relapsing-remitting multiple sclerosis. However, the relationship between Alzheimer’s disease (AD) and CNAs is unclear. A total of 36 adult participants (9 non-demented controls and 27 patients with AD) and patients with mild AD, who met the criteria for probable AD, were enrolled in the present study, which was conducted at the Department of Neurology of National Cheng Kung University Hospital. The CNA levels were increased in the plasma of patients with AD, culture medium of amyloid-β-treated SH-SY5Y cells, and plasma from a mouse model of AD. The CNA concentrations in the plasma were positively correlated with the cognitive scores. Further, CNAs in patients with AD contained neuronal tissue-specific methylated LHX2, at CpG sites 1 and 5. These results showed that the increased levels of plasma CNAs could be related to neuronal cell death that was induced by β-amyloid toxicity. Thus, the results suggested that the levels of plasma CNAs and LHX2 methylation might serve as potential biomarkers for the diagnosis of AD, particularly during the early stages of the disease.