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Background: While the association between alpha-synuclein gene promoter (Rep1) variability and risk of PD is well established, its association with cognition is unclear., Objectives: To investigate the association between Rep1 and motor and cognitive outcomes in PD., Methods: Rep1 allele lengths were determined in 172 PD patients who were grouped into "long" and "short" carriers according to previous methods. Multivariable regression analysis was performed to investigate the effect of Rep1 length on cognitive and motor scores., Results: Long Rep1 allele carriers had significantly lower MMSE (P = 0.010) and higher UPDRS Part III (P = 0.026) and H & Y (P = 0.008) scores compared to short allele carriers (controlled for age, sex, and disease duration). Interaction analyses of Rep1 with apolipoprotein 4 revealed no significant effect on clinical outcomes., Conclusions: PD patients carrying long Rep1 alleles are more impaired on cognitive and motor function independent of apolipoprotein 4 genotype. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)

We utilized ultrasensitive single molecule technology to measure plasma alpha-synuclein in 221 subjects (51 controls, 170 PD). Plasma alpha-synuclein levels were significantly higher in PD than controls (15506.3 vs. 13057.0 pg/mL, P  = 0.037), adjusting for age and gender. In PD, alpha-synuclein levels did not vary by H&Y stage or UPDRS motor scores but were significantly higher in PD patients with poorer cognition (MMSE ≤ 25) than controls ( P  = 0.016, Bonferroni corrected P  = 0.047). Alpha-synuclein levels quantified using ultrasensitive single molecule technology discriminate PD from controls and correlate with cognitive severity. These preliminary findings require independent validation to determine the utility of this assay., Competing Interests: The authors declare no financial disclosures or competing interests.