@article{9bef74baca9c4705b4b3e9c2a23d8416,
title = "Influence of medical conditions on the diagnostic accuracy of plasma p-tau217 and p-tau217/Aβ42",
abstract = "INTRODUCTION: Blood-based biomarkers (BBMs) can enable early detection of brain amyloid beta (Aβ) pathology in cognitively unimpaired individuals. However, the extent to which common medical conditions affect biomarker performance remains unclear. METHODS: Participants (n = 348) included individuals without cognitive impairment. We studied how brain Aβ associated with BBMs (Aβ42/40, phosphorylated tau [p-tau] 181 and 217, p-tau217/Aβ42, glial fibrillary acidic protein [GFAP], and neurofilament light [NfL]) and optimal BBM thresholds for predicting brain Aβ positivity and whether they are obscured by the presence of common medical conditions. RESULTS: Plasma Aβ42/40, p-tau181, p-tau217, and GFAP, but not NfL, were significantly associated with brain Aβ. P-tau217/Aβ42 showed the best discriminative performance (area under the curve: 0.91). The strength of p-tau217–brain Aβ associations were obscured by diabetes and cardiovascular conditions. DISCUSSION: These results suggest BBMs may help detect early Aβ pathology but suggest caution in their use due to common medical conditions that could affect accuracy. Highlights: Plasma Aβ42/40, p-tau181, p-tau217, and GFAP but not NfL showed significant associations with brain Aβ. BBMs were more strongly associated with the level of brain Aβ in those without diabetes and cardiovascular conditions. P-tau217/Aβ42 showed the best performance (AUC = 0.91) in discriminating Aβ presence with an optimal cut-off of >1.2, followed by p-tau217 at >0.46 pg/mL, with performance slightly improving when excluding participants with cardiovascular conditions.",
keywords = "amyloid beta, blood-based biomarkers, cardiovascular, cognitively unimpaired, diabetes, medical conditions, p-tau",
author = "Marcos Olvera-Rojas and Sewell, {Kelsey R.} and Karikari, {Thomas K.} and Haiqing Huang and Oberlin, {Lauren E.} and Xuemei Zeng and Morris, {Jill K.} and Collins, {Audrey M.} and Drake, {Jermon A.} and Sutton, {Bradley P.} and Kramer, {Arthur F.} and Hillman, {Charles H.} and Vidoni, {Eric D.} and Burns, {Jeffrey M.} and Kamboh, {M. Ilyas} and Edward McAuley and Marsland, {Anna L.} and Yijun Chen and Lafferty, {Tara K.} and Anuradha Sehrawat and Jakicic, {John M.} and Lu Wan and Chaeryon Kang and Erickson, {Kirk I.}",
note = "Dr. Karikari serves as a consultant for Quanterix Coorporation outside the submitted work. Dr. Morris has received research support from the NIH and serves on an external advisory board for the University of Kentucky CNS\u2010Met COBRE. Dr. Vidoni has received research support from the NIH and serves on an advisory board for the Vanderbilt University Alzheimer's Disease Research Center and the University of Washington Alzheimer's Disease Research Center. Dr. Burns has received research support from the NIH, research support to conduct clinical trials (paid to institution) from Eli Lilly, Amylyx, Biogen, Eisai, AbbVie, Astra\u2010Zeneca, and Roche, and has served as a consultant for Renew Research, Eisai, Eli Lilly, Labcorp, Roche, and Renew Biotechnologies. Dr. Burns serves on a data monitoring committee for Intra\u2010Cellular Therapies, Inc. Dr. Jakicic has served on a scientific advisory board for Wondr Health, Inc. The remaining authors declare no conflicts of interest. Author disclosures are available in the Supporting information . This work was supported by the National Institutes of Health (NIH) (Grant numbers: R01 AG053952, R35 AG072307), Clinical and Translational Science Institute at the University of Pittsburgh (Grant number: UL1\u2010TR\u2010001857), and Kansas University (Infrastructure Grant numbers: P30 AG072973, UL1TR002366). M.O\u2010R. is supported by the Spanish Ministry of Science, Innovation and Universities (FPU 22/02476). Funding for open access charge: Universidad de Granada / CBUA.",
year = "2025",
month = feb,
doi = "10.1002/alz.14430",
language = "English (US)",
volume = "21",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "John Wiley & Sons, Ltd.",
number = "2",
}