Changes in CSF sPDGFRβ level and their association with blood-brain barrier breakdown in Alzheimer's disease with or without small cerebrovascular lesions

Background CSF-soluble platelet-derived growth factor receptor beta (sPDGFR beta) is closely associated with pericyte damage. However, the changes in CSF sPDGFR beta levels and their role in blood-brain barrier (BBB) leakage at different stages of Alzheimer's disease (AD), with or without cerebral small vessel disease (CSVD) burden, remain unclear. Methods A total of 158 individuals from the China Aging and Neurodegenerative Disorder Initiative cohort were selected, including 27, 48, and 83 individuals with a clinical dementia rating (CDR) score of 0, 0.5, and 1-2, respectively. CSF total tau, phosphorylated tau181 (p-tau181), A beta 40, and A beta 42 were measured using the Simoa assay. Albumin and CSF sPDGFR beta were measured by commercial assay kits. CSVD burden was assessed by magnetic resonance imaging. Results CSF sPDGFR beta was the highest level in the CDR 0.5 group. CSF sPDGFR beta was significantly correlated with the CSF/serum albumin ratio (Q-alb) in the CDR 0-0.5 group (beta = 0.314, p = 0.008) but not in the CDR 1-2 group (beta = - 0.117, p = 0.317). In the CDR 0-0.5 group, CSF sPDGFR beta exhibited a significant mediating effect between A beta 42/A beta 40 levels and Q-alb (p = 0.038). Q-alb, rather than CSF sPDGFR beta, showed a significant difference between individuals with or without CSVD burden. Furthermore, in the CDR 0.5 group, CSF sPDGFR beta was higher in subjects with progressive mild cognitive impairment than in those with stable mild cognitive impairment subjects (p < 0.001). Meanwhile, CSF sPDGFR beta was significantly associated with yearly changes in MMSE scores in the CDR 0.5 group (beta = - 0.400, p = 0.020) and CDR 0.5 (A+) subgroup (beta = - 0.542, p = 0.019). Conclusions We provide evidence that increased CSF sPDGFR beta is associated with BBB leakage in the early cognitive impairment stage of AD, which may contribute to cognitive impairment in AD progression.