Peripheral Clock System Abnormalities in Patients With Parkinson's Disease

Area of Science:

• Chronobiology
• Neuroscience
• Sleep Medicine

Background:

• Parkinson's disease (PD) is frequently associated with sleep-wake disturbances.
• The role of circadian clock genes and melatonin in PD pathophysiology remains incompletely understood.

Purpose of the Study:

• To investigate peripheral clock gene expression and melatonin levels in PD patients.
• To explore correlations between these molecular markers and sleep phenotypes, particularly probable rapid eye movement sleep behavior disorder (pRBD).

Main Methods:

• Quantitative real-time PCR was used to measure the expression of five clock genes (BMAL1, CLOCK, CRY1, PER1, PER2) in peripheral blood mononuclear cells (PBMCs) from PD patients (n=326) and healthy controls (HC, n=314).
• Plasma melatonin concentrations were assessed using enzyme-linked immunosorbent assay.
• Association analyses were performed between gene expression, melatonin levels, and sleep characteristics.

Main Results:

• PD patients exhibited significantly decreased expression of all five clock genes in PBMCs compared to HC (P < 0.05).
• Plasma melatonin levels were significantly lower in PD patients than in HC (P < 0.0001).
• Reduced clock gene expression and melatonin levels were strongly associated with pRBD and excessive daytime sleepiness in PD patients (r = -0.344 to -0.789, P < 0.01).
• A combined panel of clock genes and melatonin achieved 97% diagnostic accuracy for PD with pRBD.

Conclusions:

• Peripheral clock gene expression (BMAL1, CLOCK, CRY1, PER1, PER2) and melatonin levels are significantly altered in Parkinson's disease.
• These peripheral molecular markers are associated with sleep and wakefulness disturbances in PD, including pRBD.
• Altered clock genes and melatonin may serve as potential endogenous biomarkers for sleep disturbances in PD.