Background: The accumulation of misfolded α-synuclein in the brain is associated with Parkinson's disease. However, the association between gut α-synuclein and PD and diagnostic value of α-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 α-synuclein or phosphorylated α-synuclein in patients with PD and controls. The odds ratio(OR) was pooled using random-effect models, and heterogeneity was reported as I2. 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, I2 = 72%) for gut α-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 α-synuclein.
Conclusion: Heterogeneity was high in most of the studies. This systematic review and meta-analysis confirmed a high degree of association between gut α-synuclein and PD, which suggested that gut α-synuclein is a potential therapeutic intervention. The measurement of gut α-synuclein alone could lead to the underdiagnosis of PD. Future research combining gut α-synuclein with other biochemical markers could improve the standardization of current assays.
Keywords: Enteric nervous system; Gut; Non-motor; Parkinson's disease; α-Synuclein.
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