Abstract

Background: α-synuclein (α-syn), Ser129-phosphorylated α-synuclein (p-α-syn), and neurofilament light chain (NfL) are potential biomarkers associated with cognitive impairment in Parkinson's disease (PD). This study investigates their plasma levels in relation to cognitive severity in PD.

Methods: We measured plasma α-syn, p-α-syn, and NfL levels using immunomagnetic reduction assays in 45 PD patients and 16 healthy controls. Statistical tests included Mann-Whitney U, Kruskal-Wallis, and Spearman's correlation analyses, with Bonferroni correction (α = 0.0125).

Results: Levels of α-syn and p-α-synwere significantly higher in PD compared to controls (p = 0.006 and p = 0.001, respectively; Bonferroni-adjusted p < 0.0125; Cohen's d = 1.2 and 1.5, respectively). NfL levels were elevated in PD dementia (PDD) compared to controls (p = 0.048; Cohen's d = 0.92), though this did not meet the Bonferroni-adjusted threshold of p < 0.0125. NfL levels were negatively correlated with Mini-Mental State Examination (MMSE) scores (ρ = -0.35, p < 0.0125), distinguishing PDD from controls but not from PD with normal cognition (PDNC). No significant correlations were observed between NfL levels and cognitive severity or across PD mild cognitive impairment (PDMCI) subtypes.

Conclusion: While α-syn, p-α-syn, and NfL are elevated in PD, only NfL distinguishes PDD from controls, with inconclusive ties to cognitive severity. Larger studies are needed.