The Effects of SNCA rs894278 on Resting-State Brain Activity in Parkinson's Disease

Front Neurosci. 2019 Feb 4:13:47. doi: 10.3389/fnins.2019.00047. eCollection 2019.

Abstract

The pathogenesis of Parkinson's disease (PD) is not well established. The rs894278 polymorphism of SNCA has been associated with PD. We performed this study to investigate the relationship between rs894278 and PD status on resting-state brain activity, by analyzing the amplitude of low-frequency fluctuation (ALFF). A total of 81 PD patients and 64 healthy controls were recruited. Disease severity and PD stage were evaluated in PD patients using the unified Parkinson's disease rating scale (UPDRS) and the Hoehn and Yahr (HY) scale, while the cognitive function of all participants was assessed using the mini-mental state examination (MMSE). All participants were genotyped for the rs894278 SNP and underwent a resting state functional magnetic resonance imaging scan. We found that the ALFF values of PD patients in the lingual gyrus and left caudate were lower than those of HCs; and the ALFF values for the right fusiform of participants with G allele were lower than those of participants without G allele. And we further revealed higher ALFF values in bilateral fusiform in rs894278-G carriers than in rs894278-G non-carriers in the PD group and lower ALFF values in bilateral fusiform in rs894278-G carriers than in rs894278-G non-carriers in the HC group. Our findings show that rs894278 and PD status interactively affect the brain activity of PD patients and HCs, and changes in the brain connectomes may play a key role in the pathogenesis of PD. Thus, our work sheds light on the mechanism underlying PD pathogenesis.

Keywords: ALFF; Parkinson’s disease; SNCA; brain activity; resting state functional MRI.