TY - JOUR
T1 - Saliva phosphorylated tau concentration is not associated with Alzheimer's disease, cerebrospinal fluid or blood biomarkers
AU - Gleerup, Helena Sophia
AU - Sanna, Federica
AU - Koutarapu, Srinivas
AU - Lantero-Rodriguez, Juan
AU - Montoliu-Gaya, Laia
AU - Hanrieder, Jörg
AU - Brinkmalm, Gunnar
AU - Karikari, Thomas K
AU - Simren, Joel
AU - Høgh, Peter
AU - Blennow, Kaj
AU - Hasselbalch, Steen Gregers
AU - Zetterberg, Henrik
AU - Ashton, Nicholas J
AU - Simonsen, Anja Hviid
N1 - Copyright © 2025 Gleerup, Sanna, Koutarapu, Lantero-Rodriguez, Montoliu-Gaya, Hanrieder, Brinkmalm, Karikari, Simren, Høgh, Blennow, Hasselbalch, Zetterberg, Ashton and Simonsen.
PY - 2025
Y1 - 2025
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - CSF
KW - biomarkers
KW - immunohistochemistry
KW - mass spectrometry
KW - plasma
KW - saliva
U2 - 10.3389/fnins.2025.1718237
DO - 10.3389/fnins.2025.1718237
M3 - Journal article
C2 - 41409616
SN - 1662-4548
VL - 19
SP - 1718237
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
M1 - 1718237
ER -