Evidence of Pericyte Damage in a Cognitively Normal Cohort: Association With CSF and PET Biomarkers of Alzheimer Disease

Abstract

Background: Blood-brain barrier (BBB) dysfunction is emerging as an important pathophysiologic factor in Alzheimer disease (AD). Cerebrospinal fluid (CSF) platelet-derived growth factor receptor-β (PDGFRβ) is a biomarker of BBB pericyte injury and has been implicated in cognitive impairment and AD. Methods: We aimed to study CSF PDGFRβ protein levels, along with CSF biomarkers of brain amyloidosis and tau pathology in a well-characterized population of cognitively unimpaired individuals and correlated CSF findings with amyloid-PET positivity. We performed an institutional review board (IRB)-approved cross-sectional analysis of a prospectively enrolled cohort of 36 cognitively normal volunteers with available CSF, Pittsburgh compound B PET/CT, Mini-Mental State Exam score, Global Deterioration Scale, and known apolipoprotein E (APOE) ϵ4 status. Results: Thirty-six subjects were included. Mean age was 63.3 years; 31 of 36 were female, 6 of 36 were amyloid-PET-positive and 12 of 36 were APOE ϵ4 carriers. We found a moderate positive correlation between CSF PDGFRβ and both total Tau (r=0.45, P=0.006) and phosphorylated Tau 181 (r=0.51, P=0.002). CSF PDGFRβ levels were not associated with either the CSF Aβ42 or the amyloid-PET. Conclusions: We demonstrated a moderate positive correlation between PDGFRβ and both total Tau and phosphorylated Tau 181 in cognitively normal individuals. Our data support the hypothesis that BBB dysfunction represents an important early pathophysiologic step in AD, warranting larger prospective studies.