Samuel N. Lockhart, Courtney L. Sutphen, Jordan E. Tanley, Fernando González‐Ortiz, Przemysław R. Kac, Mohamad Habes, Susan R. Heckbert, Nicholas J. Ashton, Michelle M. Mielke, Robert Koeppe, Marc D. Rudolph, Kiran K. Solingapuram Sai, Christopher T. Whitlow, Kevin D. Hiatt, Suzanne Craft, Thomas C. Register, Kathleen M. Hayden, Stephen R. Rapp, Bonnie C. Sachs, Henrik Zetterberg, K. Blennow, Thomas K. Karikari, T. Hughes
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.