Lower BCAA Levels Linked to Higher Parkinson’s Risk

A large prospective cohort study involving 374,751 participants from the UK Biobank has identified a significant association between circulating levels of branched-chain amino acids (BCAAs) and the risk of developing Parkinson’s disease (PD). Published in npj Parkinson’s Disease, the research indicates that higher baseline levels of total BCAAs, leucine, and valine were associated with a lower risk of incident PD. The study, led by Zhiqing Chen and colleagues, utilized Cox proportional hazards models to estimate these associations, revealing approximately linear inverse dose-response relationships. This finding suggests that altered BCAA metabolism may serve as a prediagnostic metabolic feature of the disease, offering a potential avenue for further biological and translational investigation.

The role of circulating branched-chain amino acids in Parkinson’s disease remains unclear. To characterize prediagnostic patterns and related biological signatures, the investigators analyzed data from participants who were free of PD and other neurodegenerative diseases at the baseline assessment. The study employed restricted cubic splines to assess dose-response relationships and LOESS smoothing to model control-standardized pseudotemporal patterns of baseline BCAA levels according to the time to PD diagnosis.

Key findings from the analysis showed that baseline BCAA levels were lower among participants assessed at time points closer to their subsequent PD diagnosis. Furthermore, the study utilized fully adjusted linear regression models to evaluate the associations between BCAAs and various PD-related biomarkers. The results indicated that higher BCAA levels were associated with lower PhenoAge acceleration, lower levels of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NEFL), and more favorable white matter microstructural profiles derived from diffusion MRI.

The study’s scope was limited to participants in the UK Biobank who did not have PD or other neurodegenerative diseases at the start of the study, ensuring a clear baseline for assessing incident cases. However, as an observational study, the results establish associations rather than causal links. The authors emphasize that while altered BCAA metabolism may represent a prediagnostic feature, further research is required to determine the biological mechanisms and translational relevance of these findings.

Subject of Research: Association between circulating branched-chain amino acids and incident Parkinson's disease risk in a prospective cohort study

Article Title: Circulating branched-chain amino acids and multimodal signatures of incident Parkinson’s disease: a prospective cohort study

Article References: Chen, Z., Zhang, B., Huang, C., Lu, L., Yin, J., Zhang, Y., & Huang, Y. (2026). Circulating branched-chain amino acids and multimodal signatures of incident Parkinson’s disease: a prospective cohort study. npj Parkinson's Disease. https://doi.org/10.1038/s41531-026-01633-z

Image Credits: AI Generated

DOI: 10.1038/s41531-026-01633-z

Keywords: Parkinson's disease, branched-chain amino acids, UK Biobank, prospective cohort study, neurodegenerative biomarkers, metabolic signatures, Circulating, branched-chain, amino, acids, multimodal, signatures