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.
Highlights
Parkinson’s disease is a common neurodegenerative disease that affects 1.7% of Chinese population over the age of 65 (Zhang et al, 2005)
There were no significant differences in the age of onset, course of disease, scores for unified Parkinson’s disease rating scale (UPDRS), UPDRS I, UPDRS II, UPDRS III, UPDRS IV, tremor, rigidity, bradykinesia, or posture/gait, Hoehn and Yahr scale (HY) scale stage, or levodopa equivalent daily dose (LEDD) between rs894278-G carriers and non-carriers among Parkinson’s disease (PD) patients (Table 2)
Our results show that the amplitude of low-frequency fluctuation (ALFF) values of PD patients in the lingual gyrus and the left caudate were lower than those of healthy controls (HCs), and that the ALFF value of participants with G allele in the right fusiform were lower than those of participants without G allele
Summary
Parkinson’s disease is a common neurodegenerative disease that affects 1.7% of Chinese population over the age of 65 (Zhang et al, 2005). The remaining polymorphisms either do not directly contribute to PD and work in concert with other genetic variants or explain only a minute portion of disease pathology. In both cases, identified variants maintain the ability to be protective against or contribute to PD pathology (Guo et al, 2015). Rare mutations in SNCA can cause PD that follows Mendelian inheritance patterns, but this does not appear to be a common cause of PD in the Han population (Deng et al, 2015). Many common variants of SNCA, including rs894278, contribute to PD risk and help to explain the appearance of PD in non-mendelian patterns (Xu W. et al, 2015). A strong link between rs894278 and PD has been uncovered, the mechanism governing the impact of rs894278 on PD has yet to be elucidated
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