Diagnostic utility of gut α-synuclein in Parkinson's disease: A systematic review and meta-analysis

Background: The accumulation of misfolded alpha-synuclein in the brain is associated with Parkinson's disease. However, the association between gut alpha-synuclein and PD and diagnostic value of alpha-synuclein in the gut still remain controversial. Methods: A literature search from inception to June 2018 was conducted, yielding 21 studies eligible for a systematic review and meta-analysis. We included studies that reported data on gut alpha-synuclein or phosphorylated alpha-synuclein in patients with PD and controls. The odds ratio(OR) was pooled using random-effect models, and heterogeneity was reported as I-2. Studies were assessed for quality using the Newcastle-Ottawa Scale. Sensitivity and specificity analyses were performed using the summary receiver operating characteristics curve approach. Results: The database search yielded 395 results, of which 21 studies were deemed relevant. The PD group had a pooled OR of 10.01 (95% CI: 3.15-31.82, I-2 = 72%) for gut alpha-synuclein compared with the control group. Sensitivity and specificity for distinguishing PD from controls were 0.568 and 0.819, respectively, for the colon, and 0.579 and 0.822, respectively, for phosphorylated alpha-synuclein. Conclusion: Heterogeneity was high in most of the studies. This systematic review and meta-analysis confirmed a high degree of association between gut alpha-synuclein and PD, which suggested that gut alpha-synuclein is a potential therapeutic intervention. The measurement of gut alpha-synuclein alone could lead to the underdiagnosis of PD. Future research combining gut alpha-synuclein with other biochemical markers could improve the standardization of current assays.