Abstract
<title>Abstract</title> <p> Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the neutrophil-to-lymphocyte ratio (NLR) are routinely measured; lower ALT and higher NLR have been reported in Parkinson's disease (PD), but longitudinal evidence remains limited. In this prospective cohort study, we analyzed longitudinal data from the BEAT-PD cohort, comparing 175 individuals with PD (63 idiopathic, 51 <italic>LRRK2</italic> -PD, 61 <italic>GBA1</italic> -PD) to 345 non-manifesting individuals (74 <italic>LRRK2</italic> , 94 <italic>GBA1</italic> , 177 healthy controls). ALT was consistently lower in PD and declined longitudinally, while increasing slightly in controls over a median 4-year follow-up. Lower ALT was associated with longer disease duration independent of dopaminergic medication dosage, suggesting the decline may reflect disease biology rather than a pharmacological effect. AST and NLR differences were less consistent. Analyte levels did not differ significantly across genetic PD subgroups. These findings support ALT as a candidate biomarker of PD risk and progression, though effect sizes were small and not currently clinically actionable. </p>