Plasma and neuroimaging biomarkers of small vessel disease and Alzheimer's disease in a diverse cohort: MESA

INTRODUCTION: Little is known about how Alzheimer's disease (AD) plasma biomarkers relate to cerebral small vessel disease (cSVD) neuroimaging biomarkers. METHODS: The study involved 251 Wake Forest Multi-Ethnic Study of Atherosclerosis (MESA) Exam 6 participants with plasma AD biomarkers, magnetic resonance imaging, amyloid positron emission tomography (PET), and adjudicated cognitive status. Multivariable models examined cross-sectional relationships between plasma and neuroimaging biomarkers, considering comorbidities. RESULTS: Lower amyloid beta (Aβ) 42/Aβ40 and higher glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau at threonine 217 (p-tau217) were associated with greater neurodegeneration. Lower plasma Aβ42/Aβ40 and higher p-tau217 and p-tau231 were associated with greater Aβ PET deposition. NfL was positively associated with white matter hyperintensities (WMH) and white matter (WM) free water. P-tau measures were positively associated with WM free water. Lower Aβ42/Aβ40 was associated with the presence of microbleeds. GFAP was positively associated with WMH. DISCUSSION: We observed expected associations of plasma biomarkers with cognitive status and imaging biomarkers. GFAP, NfL, p-tau181, p-tau217, and p-tau231 are associated with cSVD in addition to AD-related pathology.