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 (sPDGFRβ) is closely associated with pericyte damage. However, the changes in CSF sPDGFRβ 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), Aβ40, and Aβ42 were measured using the Simoa assay. Albumin and CSF sPDGFRβ were measured by commercial assay kits. CSVD burden was assessed by magnetic resonance imaging.

Results: CSF sPDGFRβ was the highest level in the CDR 0.5 group. CSF sPDGFRβ was significantly correlated with the CSF/serum albumin ratio (Q-alb) in the CDR 0-0.5 group (β = 0.314, p = 0.008) but not in the CDR 1-2 group (β = - 0.117, p = 0.317). In the CDR 0-0.5 group, CSF sPDGFRβ exhibited a significant mediating effect between Aβ42/Aβ40 levels and Q-alb (p = 0.038). Q-alb, rather than CSF sPDGFRβ, showed a significant difference between individuals with or without CSVD burden. Furthermore, in the CDR 0.5 group, CSF sPDGFRβ was higher in subjects with progressive mild cognitive impairment than in those with stable mild cognitive impairment subjects (p < 0.001). Meanwhile, CSF sPDGFRβ was significantly associated with yearly changes in MMSE scores in the CDR 0.5 group (β = - 0.400, p = 0.020) and CDR 0.5 (A+) subgroup (β = - 0.542, p = 0.019).

Conclusions: We provide evidence that increased CSF sPDGFRβ is associated with BBB leakage in the early cognitive impairment stage of AD, which may contribute to cognitive impairment in AD progression.