Plasma platelet-derived growth factor receptor-β decrease correlates with blood-brain barrier damage in Alzheimer's disease.

Li J, Li A, Ye C, Zhang L, Jiang M et al.

Mol Neurodegener 2026

BACKGROUND: The blood-brain barrier (BBB) damage is frequently observed in Alzheimer’s disease (AD). However, it remains unclear whether plasma platelet-derived growth factor receptor-β (PDGFRβ) level is related to BBB damage and how it correlates with AD core pathologies, neurodegeneration, and cognitive decline. METHODS: In this study, we measured cerebrospinal fluid (CSF) albumin, plasma albumin, and plasma PDGFRβ concentrations for 93 participants with paired CSF and plasma samples. We investigated the association between CSF/Plasma albumin ratio (Qalb) and plasma PDGFRβ. Subsequently, plasma PDGFRβ, phosphorylated tau (p-Tau) 217 (p-Tau217), p-Tau231, and N-terminal tau (NT1-tau) concentrations were measured in 592 participants. Of them, 519, 278, 152, 470, and 586 participants underwent testing for plasma p-Tau181, Amyloid-β (Aβ) positron emission tomography (PET), tau PET, structural magnetic resonance imaging (MRI), and MoCA, respectively. Additionally, 154 and 210 had longitudinal MRI and cognition data. We investigated the association between plasma PDGFRβ and baseline Aβ and tau PET, as well as the baseline and slope of temporal-MetaROI cortical thickness and MoCA. We did these analyses separately for the whole cohort, females, and males. RESULTS: Plasma PDGFRβ was associated with Qalb in the whole cohort (standardized β = − 0.218 [95% confidence interval: − 0.412, − 0.024], DISCUSSION: This study demonstrated that decreased plasma PDGFRβ levels are associated with BBB damage, Aβ plaques, tau tangles, neurodegeneration, and cognitive decline in AD, and modulate the relationship between plasma tau biomarkers and both longitudinal neurodegeneration and cognitive decline. These findings suggest a potential plasma biomarker for detecting and monitoring BBB leakage in AD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13024-026-00926-4.