AUTHOR=Gleerup Helena Sophia , Sanna Federica , Koutarapu Srinivas , Lantero-Rodriguez Juan , Montoliu-Gaya Laia , Hanrieder Jörg , Brinkmalm Gunnar , Karikari Thomas K. , Simren Joel , Høgh Peter , Blennow Kaj , Hasselbalch Steen Gregers , Zetterberg Henrik , Ashton Nicholas J. , Simonsen Anja Hviid 

TITLE=Saliva phosphorylated tau concentration is not associated with Alzheimer’s disease, cerebrospinal fluid or blood biomarkers

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 19 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1718237

DOI=10.3389/fnins.2025.1718237

ISSN=1662-453X

ABSTRACT=ObjectiveOne of the most challenging aims of the scientific community in the last decade, is to find an easily accessible matrix in which neurodegeneration-related biomarkers can be measured and used to diagnose Alzheimer’s disease (AD) in vivo. Blood biomarkers have led the way in this regard, specifically, phosphorylated tau (p-tau) which demonstrates excellent diagnostic and prognostic properties. The recent success of the blood biomarkers for AD pathophysiology poses a new question – can p-tau be measured in other peripheral and even more accessible biofluids, and do they have relation to disease? Saliva contains biomarkers linked to neurodegeneration and it has been proposed as a potential sample type that would be minimally invasive to collect for this purpose.MethodsIn this study, we confirmed the presence of several p-tau species in saliva fluid and saliva gland tissue by Immunoprecipitation-Mass spectrometry (IP-MS) and immunohistochemistry, respectively. Furthermore, we measured saliva and plasma p-tau181 concentrations in 125 memory clinic participants, using ultrasensitive Single molecule array (Simoa) technology.ResultsDespite a weak correlation between saliva p-tau181 and CSF t-tau (rho = 0.13, p < 0.01), there were no significant differences in saliva p-tau181 concentration between the different clinical groups and the healthy controls.InterpretationFor this reason, we conclude that saliva p-tau181 is not acceptable as a biomarker for AD.