Elevated levels of circulating plasma sPDGFRβ in cognitively impaired APOE4 carriers

Increased levels of cerebrospinal fluid (CSF) soluble platelet-derived growth factor receptor-β (sPDGFRβ), a marker of blood-brain barrier (BBB)-associated pericyte cell injury, have been shown to correlate with increased BBB permeability and severity of Alzheimer's disease (AD) pathology. It has been also shown that increased CSF sPDGFRβ levels can predict cognitive dysfunction in APOE4 carriers bearing the main susceptibility gene for AD. Whether plasma sPDGFRβ levels are also elevated in APOE4 carriers has not been explored. Here, we analyzed plasma samples for sPDGFRβ levels, Ab_42/40 ratio, and pTau217 in 115 APOE3 homozygotes and APOE4 carriers with Clinical Dementia Rating (CDR) score of 0 and 0.5. Our data show that plasma sPDGFRβ levels are increased in APOE4 carriers with cognitive impairment compared to APOE4 carriers that are cognitively unimpaired as well as relative to cognitively impaired APOE3 carriers even after controlling for plasma Aβ_42/40 ratio and pTau217. Thus, our data suggest that plasma sPDGFRβ is a useful biomarker of brain pericytes/BBB damage in APOE4 carriers.