Cerebrospinal fluid (CSF) soluble platelet-derived growth factor receptor-β (sPDGFRβ) has emerged as a promising biomarker of pericyte injury and blood–brain barrier (BBB) dysfunction in Alzheimer's disease (AD). However, evidence regarding its relationship with AD pathology and cognitive decline has remained fragmented. We conducted a systematic review and meta-analysis to evaluate the association of CSF sPDGFRβ with BBB dysfunction, tau pathology, cognitive performance, and longitudinal cognitive decline.

Six eligible studies involving 699 participants across the Alzheimer's disease continuum were included. Correlation-based outcomes were synthesized using Fisher-z transformation, while regression-based outcomes were pooled using generic inverse-variance models. Higher CSF sPDGFRβ was consistently associated with greater BBB dysfunction (I² = 0%; Z = 8.65, p < 0.00001), increased tau pathology (I² = 0%; Z = 5.71, p < 0.00001), worse cross-sectional cognitive performance (Z = 4.41, p < 0.0001), and faster longitudinal cognitive decline (Z = 3.13, p = 0.002). Associations were particularly pronounced in biomarker-positive or clinically affected participants, supporting a disease-specific neurovascular signal rather than age-related changes.

These findings provide quantitative evidence that CSF sPDGFRβ is a robust biomarker linking BBB dysfunction with tau-mediated neurodegeneration and cognitive decline. The results support further evaluation of sPDGFRβ as an early biomarker for patient stratification, disease monitoring, and therapeutic targeting in Alzheimer's disease.

Keywords: Alzheimer's disease; blood–brain barrier; cerebrospinal fluid; sPDGFRβ; pericyte injury; tau pathology; cognitive decline; neurovascular dysfunction; biomarker; meta-analysis.