Mid-life candidate vascular plasma biomarkers are associated with MRI markers of vascular brain injury and amyloid- and tau-PET in cognitively healthy adults
Abstract
Background Identifying candidate biomarkers for preclinical dementia could improve our understanding of underlying biological pathways leading to vascular brain injury (VBI) and neurodegeneration. Objective To identify plasma protein markers of MRI markers of VBI and amyloid- and tau-PET burden in cognitively healthy adults. Methods 125 plasma proteins were measured in dementia-free Framingham third Generation cohort participants between 2002–2005 (mean age 46 [SD 8]) with available MRI brain (n = 1039), 11C-Pittsburgh Compound-B (PiB)- (n = 279), and/or 18F-Flortaucipir (FTP)-PET (n = 239) performed ∼13–15 years after blood sampling. Outcomes included white matter hyperintensities, peak width of skeletonized mean diffusivity, and free water); precuneus-, posterior cingulate- and frontal, lateral and retrosplenial cortices-Aβ deposition; and global- and entorhinal cortex-tau. Results Growth differentiation factor-15 (GDF-15) was associated with increased VBI (p ≤ 0.02), while soluble receptor for advanced glycation end products (sRAGE) and insulin-like growth factor 1 (IGF-1) were associated with reduced VBI (p ≤ 0.04). Plasma tau, renin, and ApoB were associated with increased Aβ deposition (p ≤ 0.02), while sRAGE was associated with reduced Aβ deposition in all regions (p ≤ 0.03). Brain natriuretic peptide (NT-proBNP) and purine nucleoside phosphorylase (PNP) were associated with increased tau deposition (p ≤ 0.02), while low density lipoprotein cholesterol (LDL-C) and GDF-15 were associated with reduced tau deposition (p ≤ 0.04). Conclusions Candidate vascular plasma proteins measured in dementia-free, asymptomatic adults at late mid-life were associated with subsequent neuroimaging markers of VBI and tau and amyloid deposition. Our findings highlight potential novel candidate vascular biomarkers for preclinical dementia but will require validation.