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Metabolic factors associated with plasma phosphorylated tau analytes used to detect Alzheimers disease pathology

Yang, K. L.; Ma, Y.; Ennis, G.; Jonaitis, E. M.; Rea Reyes, R. E.; Johnson, S. C.; Ashton, N. J.; Blennow, K.; Zetterberg, H.; Bendlin, B. B.

2025-07-28 geriatric medicine
10.1101/2025.07.27.25332280 medRxiv
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STRUCTURED ABSTRACTO_ST_ABSINTRODUCTIONC_ST_ABSThe interpretation of plasma phosphorylated tau (pTau) levels may be influenced by metabolic conditions, such as insulin resistance (IR), type 2 diabetes mellitus (T2DM), obesity, and kidney function. We examined the extent to which metabolic factors are associated with plasma pTau concentrations (pTau181, pTau217, pTau231) and the contribution of these factors on analytical outcomes. METHODSWe analyzed data from 287 participants using partial Spearmans rho, Mann Whitney U, ROC analysis, and linear mixed models. RESULTSConcordance between plasma pTau217 and amyloid PET was not influenced by IR or estimated-glomerular-filtration-rate (eGFR). Accounting for eGFR improved concordance of pTau181 and pTau231 with amyloid PET. Age, binarized waist-to-hip ratio, and amyloid status were associated with all longitudinal pTau concentrations, and eGFR associated with longitudinal pTau231. DISCUSSIONMetabolic health may influence the interpretation of some plasma pTau biomarkers, potentially necessitating adjustments for metabolic factors in research and clinical settings.

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