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

Front Neurosci. 2025 Dec 2;19:1718237. doi: 10.3389/fnins.2025.1718237. eCollection 2025.

ABSTRACT

OBJECTIVE: One 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.

METHODS: In 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.

RESULTS: Despite 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.

INTERPRETATION: For this reason, we conclude that saliva p-tau181 is not acceptable as a biomarker for AD.

PMID:41409616 | PMC:PMC12705599 | DOI:10.3389/fnins.2025.1718237