Abstract
Objective: This study assessed the methylation of peripheral NCAPH2 in individuals with subjective cognitive decline (SCD), identified its correlation with the hippocampal volume, and explored whether the correlation is influenced by apolipoprotein E ε4 (APOE ε4) status.Methods: Cognitively normal controls (NCs, n = 56), individuals with SCD (n = 81), and patients with objective cognitive impairment (OCI, n = 51) were included from the Sino Longitudinal Study on Cognitive Decline (NCT03370744). All participants completed neuropsychological assessments, blood tests, and structural MRI. NCAPH2 methylation was compared according to the diagnostic and APOE ε4 status. Partial correlation analysis was conducted to assess the correlations between the hippocampal volume, cognitive tests, and the NCAPH2 methylation levels.Results: Individuals with SCD and patients with OCI showed significantly lower levels of NCAPH2 methylation than NCs, which were independent of the APOE ε4 status. The NCAPH2 methylation levels and the hippocampal volumes were positively correlated in the SCD APOE ε4 non-carriers but not in the OCI group. No association was found between the NCAPH2 methylation levels and the cognitive function.Conclusion: Abnormal changes in blood NCAPH2 methylation were found to occur in SCD, indicating its potential to be used as a useful peripheral biomarker in the early stage of Alzheimer's disease screening.
Highlights
Alzheimer’s disease (AD) is a progressive and highly debilitating neurodegenerative disorder, accounting for about two-thirds of 50 million people with dementia worldwide (Lane et al, 2018)
Subjective cognitive decline (SCD) is defined using the following criteria (Jessen et al, 2014): (1) self-experienced persistent decline in memory rather than other domains of cognition within the last 5 years; (2) concerns related to SCD and a feeling of worsened performance when compared to others of the same age group; and (3) performance on standardized cognitive tests within age, gender, and education-adjusted norms and failure to meet the criteria for MCI or dementia
The Hamilton Anxiety Scale (HAMA) score was higher among the patients with objective cognitive impairment (OCI) than among the controls (F = 4.06, p = 0.019), but there was no difference between the SCD and control
Summary
Alzheimer’s disease (AD) is a progressive and highly debilitating neurodegenerative disorder, accounting for about two-thirds of 50 million people with dementia worldwide (Lane et al, 2018). Blood NCAPH2 Methylation in SCD body of evidence points to the epigenetic contribution of AD, and both global and gene-specific changes in DNA methylation have been observed in the affected postmortem brain regions (Bakulski et al, 2012; De Jager et al, 2014; Cronin et al, 2017). The search for peripheral blood epigenetic biomarkers of AD is of particular interest because of the unavailability of brain DNA samples until postmortem and the inability to collect longitudinal brain samples to track disease diagnosis (Bakulski et al, 2016). Peripheral blood DNA methylation levels in the NCAPH2/LMF2 promoter region were significantly decreased in patients with AD and those with amnestic mild cognitive impairment (aMCI) (Kobayashi et al, 2016); these are considered to be a potentially useful biomarker for the diagnosis of AD. There have been relatively few studies devoted to the determination of NCAPH2 methylation patterns in peripheral blood in the early stages of AD
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