Genetic and clinical investigation of insulin-degrading enzyme in Parkinson’s disease within the Chinese Han population

Introduction Growing evidence suggests a mechanistic link between type 2 diabetes mellitus and Parkinson’s disease (PD), with insulin-degrading enzyme (IDE) implicated in both insulin and amyloid-β metabolism, as well as α-synuclein degradation. However, the role of IDE in PD pathogenesis remains insufficiently defined. This study aimed to investigate the association of IDE gene polymorphisms and serum IDE levels with sporadic PD in a Chinese Han population. Methods Fourteen single nucleotide polymorphisms (SNPs) within the IDE gene were genotyped in 463 patients with sporadic PD and 576 age- and sex-matched healthy controls (HCs). An independent cohort of 100 PD patients and 100 HCs was used to quantify serum IDE concentrations. Correlations between IDE levels and clinical features were assessed. Logistic regression was employed to identify independent factors associated with PD. Results Among the examined SNPs, rs11187007 showed a nominal allelic association with PD ( P = 0.046), which did not survive the Bonferroni correction. Serum IDE concentrations were significantly higher in PD patients than in HCs ( P = 0.015). Elevated IDE levels were negatively correlated with Mini-Mental State Examination scores ( R = –0.230, P = 0.027) and positively associated with more severe symptoms. Logistic regression indicated that elevated serum IDE levels were associated with PD. Conclusion Our findings highlight that elevated serum IDE correlates with PD, suggesting a role for IDE in neurodegeneration, warranting further mechanistic and longitudinal studies to evaluate its potential as a therapeutic target in PD.