Synergistic blood-based diagnostic value of AP3B1 and BMPR2 in Parkinson’s disease

Reliable blood-based biomarkers for Parkinson's disease (PD) are needed for minimally invasive diagnosis. We identified a synergistic mRNA biomarker pair, AP3B1 and BMPR2, detectable in blood through an integrative multi-omics workflow. DEGs from a meta-analysis of PD versus healthy controls (HCs) were intersected with DEG-enriched pathway genes and analysed via three-step SMR to identify PD risk candidates, from which machine learning (SVM-RFE and random forest) prioritized AP3B1 and BMPR2. Knockdown of each gene in SH-SY5Y-derived neurons reproduced Parkinsonian phenotypes, with protein docking and co-immunoprecipitation suggesting a direct interaction. An XGBoost model built on PPMI blood RNA-seq (n = 2585) using 25 established PD biomarkers (baseline AUC ~ 0.595) improved to 0.745 with addition of both AP3B1 and BMPR2. qRT-PCR in a cohort of clinical blood samples confirmed their downregulation in PD. These findings support AP3B1 and BMPR2 as a synergistic biomarker pair with speculative biological relevance and possible translational potential.