Retrospective analysis of 1,315 PPMI participants found a nonlinear association between serum AST/ALT ratio and familial versus sporadic PD—strong above a threshold of 1.503—with a predictive model AUC of 0.758.

AST/ALT is an inexpensive, routinely available serum marker that could aid PD subtyping and trial stratification, offering translational potential despite limited mechanistic insight and the need for prospective validation.

BACKGROUND: Parkinson's disease (PD) exhibits genetic heterogeneity with varying clinical presentations. The aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio has emerged as a potential indicator of neurodegenerative processes, yet its relationship with PD genetic subtypes remains unexplored. OBJECTIVE: This study aims to investigate the relationship between the AST to ALT ratio (AST/ALT) and different genetic subtypes of PD. METHODS: This retrospective analysis included 1315 PD patients (1005 sporadic, 310 familial) from Parkinson's Progression Markers Initiative (PPMI) databases. Multivariable logistic regression models, restricted cubic splines, and inflection point analysis were employed to assess the relationship between the AST/ALT ratio and genetic subtypes of PD, adjusting for demographic, clinical, and biochemical covariates. Subgroup and sensitivity analyses were conducted to evaluate robustness, and a predictive model was developed using stepwise selection. RESULTS: Compared with sporadic PD (adjusted odds ratio [OR] 1.69, 95% confidence interval 1.19-2.39, p = 0.003). A nonlinear relationship was identified (nonlinearity p = 0.002), with an inflection point at 1.503. Above this threshold, the association became markedly stronger (OR 22.27, p = 0.0007), whereas no significant association was detected below it. Findings remained consistent across all subgroup and sensitivity analyses. A predictive model incorporating the AST/ALT ratio, along with clinical and demographic factors, achieved a moderate discriminatory ability (area under the curve 0.758). CONCLUSIONS: The AST/ALT ratio demonstrates a significant, nonlinear association with genetic subtypes of PD, particularly among individuals with higher ratio values. This readily accessible serum marker may hold promise for refining PD subtyping and informing personalized management strategies, warranting validation in prospective and diverse cohorts.