Rab proteins as diagnostic biomarkers for Parkinson’s disease: a systematic review
Abstract
Purpose: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. PD is typically diagnosed at late-stage, concurrent with loss of up to 70% of these neurons so patient care could be improved by diagnosis at prodromal stages. The occurrence of Parkinsonian-like diseases also understores the importance of accurate differential diagnosis, yet no biomarkers are currently used in clinical settings to minimize diagnostic errors. The Rab family of GTPases has been implicated in the PD pathogenesis, with protein levels elevated in pre-clinical models. This review evaluates the utility of Rab proteins as a biomarker for PD. Methods: A systematic search was performed following PRISMA guidelines using PubMed, Scopus, Cochrane, SAGE, OVID and Web of Science (references up to November 2025). Search keywords included: "Parkinson", "Rab" and "biomarker". Results: Out of 1404 records identified, 27 articles were sought for retrieval after duplicate removal and title/abstract screening. The search yielded 13 articles that fit the inclusion criteria. 8 different Rab proteins of interest and/or their phosphorylated forms were reported as differentially expressed in PD patients in these papers. Of the 8 Rab proteins, Rab35 had a consistent elevation. However, this was observable from a single research group, presenting the need for independent validation of Rab35 as a diagnostic biomarker for idiopathic PD (iPD). In contrast, though preliminary, pRab10 may have relevance for patient stratification and monitoring drug response in PD patients. However, with the small evidence base, further research with larger sample sizes, patient sub-types and other contributing factors will be vital before integration into clinical practice. Conclusion: Overall, the evidence for Rab proteins as diagnostic biomarkers is emerging rather than established. Inconsistent reporting, small and frequently overlapping samples prevented quantitative synthesis.