sPDGFRβ and neuroinflammation are associated with AD biomarkers and differ by race: The ASCEND Study

Abstract

Introduction: There remains an urgent need to identify preclinical pathophysiological mechanisms of Alzheimer's disease (AD) development in high-risk, racially diverse populations. We explored the relationship between cerebrospinal fluid (CSF) markers of vascular injury and neuroinflammation with AD biomarkers in middle-aged Black/African American (B/AA) and non-Hispanic White (NHW) participants.

Methods: Adults (45-65 years) with a parental history of AD were enrolled (n = 82). CSF and blood biomarkers were collected at baseline and year 2.

Results: CSF total tau (t-tau), phosphorylated tau (p-tau), and amyloid beta (Aβ)40 were elevated at year 2 compared to baseline. CSF soluble platelet-derived growth factor receptor β (sPDGFRβ) levels, a marker of pericyte injury, correlated positively with t-tau, p-tau, Aβ40 markers of vascular injury, and cytokines at baseline and year 2. CSF sPDGFRβ and tau were significantly lower in B/AA than NHW.

Discussion: Vascular dysfunction and neuroinflammation may precede cognitive decline and disease pathology in the very early preclinical stages of AD, and there are race-related differences in these relationships.

Highlights: Cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers changed over 2 years in high-risk middle-aged adults. Markers of vascular dysfunction were associated with the CSF biomarkers amyloid beta and tau. AD biomarkers were lower in Black compared to non-Hispanic White individuals. Markers of vascular dysfunction were lower among Black individuals.

Keywords: Alzheimer's disease; parental history; prevention; tau; vascular risk.