Abstract
With new pharmaceutical treatments for Alzheimer’s Disease (AD) potentially most effective in the preclinical stage, research has focused on accessible preclinical biomarkers of AD. Recently, phosphorylated tau-181 (pTau181) from plasma has emerged as a leading candidate for the early detection of preclinical AD, possibly decades before symptoms become apparent. Understanding how comorbidities and confounding factors affect plasma pTau181 levels is crucial for clinical interpretation of biomarker outcomes. Kidney function and cardiometabolic risk factors may influence peripheral plasma biomarkers, yet studies confirming this association are currently inconclusive. This cross-sectional study aims to determine associations of plasma pTau181 with cardiometabolic risk factors, including metabolic syndrome, retinal microvasculature, and kidney function, in middle-aged participants.
pTau181 and cardiometabolic data were analysed at age 45 from 417 of the 938 members (54% female) of the Dunedin Multidisciplinary Health and Development Study with available pTau181 data. Participants were primarily New Zealand European (Pākehā). Plasma pTau181 concentrations were quantified from plasma using Quanterix Simoa SR-X platform. Linear regression was used to assess associations between pTau181 and cardiometabolic risk factors.
Kidney function (eGFR) was associated with pTau181 concentrations (B = -0.006, P <.001), even after adjusting for sex and APOEε4 status. Despite the known links between cardiometabolic risk and AD, no other associations were evident at this early age. As such, results suggest kidney dysfunction may potentially affect protein clearance, thus increasing levels of pTau181. However, further assessment of the association between eGFR and pTau181 is essential for advancing research into plasma biomarkers of AD and their use in clinical trials and treatment plans. Longitudinal studies with ethnically diverse participants are necessary to better understand this association and determine the significance of considering renal function in the interpretation of pTau181 within the broader ageing population.