Parkinson's disease (PD) is a common neurodegenerative disease among the elderly, affecting approximately 2% of the population over 60 years old. The main symptoms in patients include tremors in the limbs, rigidity, bradykinesia, and postural instability. PD is a multifactorial disease, closely associated with both environmental and genetic factors.

PD patients can primarily be classified into two groups. The major group, which constitutes about 60-70% of PD patients, shows degeneration mainly in the dopaminergic neurons of the substantia nigra in the midbrain. In idiopathic PD, most patients exhibit sufficient clinical manifestations, and by the time they are diagnosed, they have already lost 60-70% of their dopaminergic neuronal function.

Various early motor neuron-related biomarkers are actively being studied to evaluate their potential to identify early PD or patients at risk of developing PD. These include clinical measurements (rapid eye movement behavior disorder, olfactory deficits, mood disorders), molecular measurements (α-synuclein in cerebrospinal fluid and blood), and brain imaging methods.

In various studies, epigenetic mechanisms have also become important factors in the molecular etiology of neurodegenerative diseases, including PD. Research indicates that low methylation of the promoter region of the α-synuclein gene (SNCA) has been found in the substantia nigra of PD patients. Moreover, this SNCA promoter hypomethylation has increased SNCA protein expression in cell cultures, potentially contributing to PD pathology. It has also been confirmed that L-dopa therapy is associated with high methylation of the SNCA promoter, suggesting that current PD treatments may involve changes in methylation levels. Although other studies with smaller cohorts have not consistently observed changes in SNCA methylation in PD, epigenomic changes in other genes associated with PD, such as hypomethylation of NPAS2 and CYP2E1 and hypermethylation of PGC1-α and Tau (MAPT) H1 haplotype, are also relevant to PD.

In a clinical study involving 219 PD patients and 223 controls, two CpG sites were found to exhibit abnormal methylation. Another study using blood DNA samples from 335 PD patients and 237 controls conducted an epigenome-wide association study (EWAS) and identified 82 CpG sites with abnormal DNA methylation in PD patients. In another research project, blood samples from 189 PD patients and 191 controls were collected and followed up for a period ranging from 0.8 to 11.98 years. Statistical results indicated similar disease progression in early or mild PD patients over an average of 3.7 years. Longitudinal DNA methylation studies in PD patients showed that changes in the methylation level of the CYB21 gene were highly correlated with PD progression, and dopamine therapy was indeed found to affect DNA methylation changes in PD patients.

These studies repeatedly demonstrate significant changes in the methylation level of PD patients in both brain and blood tissues. These changes are also associated with disease progression and medication treatment. Specific biomarkers can be used as detection targets based on differences in methylation levels.

Ref.
1.Henderson-Smith, A. et al. (2019) ‘DNA methylation changes associated with Parkinson’s disease progression: outcomes from the first longitudinal genome-wide methylation analysis in blood’, Epigenetics, 14(4), pp. 365–382. doi: 10.1080/15592294.2019.1588682.

2.Chuang YH, Paul KC, Bronstein JM, et al. Parkinson’s disease is associated with DNA methylation levels in human blood and saliva. Genome Med. 2017;9(1):76