Salivary total tau: a clinically practical measure of tau neuropathology in Alzheimer’s disease

Neurofibrillary tangles, consisting of intracellular accumulations of the protein tau, are a hallmark feature of Alzheimer's disease (AD), and are thought to contribute to neuronal dysfunction and death during the disease process. The quantification of tau proteins in cerebrospinal fluid (CSF) or plasma has enormous utility for AD diagnosis; however, validated non-invasive measures of tau protein are lacking and would have added value for widespread screening. In this study, we quantified the levels of total tau (t-tau), along with neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), in saliva samples from 111 participants, including those with CSF biomarker-confirmed AD, mild AD, non-AD cognitively impaired (CI) and cognitively unimpaired (CU) older adults, using immunoassays on the Meso Scale Discovery platform. We find that salivary levels of t-tau were significantly elevated in AD and mild AD, but not other CI patients, compared to CU adults, while salivary levels of NfL and GFAP showed no significant differences across cohorts. In addition, we found that salivary t-tau was significantly correlated with CSF biomarker measures, including significant positive correlations with CSF t-tau and p-tau 181 (0.257; p = 0.016 and 0.276; p = 0.009 for t-tau and p-tau 181, respectively). Salivary t-tau was also found to predict AD cases compared to CU individuals with an area under the curve of 0.834 (95% CI 0.74-0.93; p < 0.0001). Finally, we observed that salivary t-tau levels were significantly negatively correlated with cognitive performance in AD patients, as well as all individuals together. These findings suggest that salivary t-tau might represent a non-invasive biomarker specific to AD pathology and could aid in early detection of AD or for clinical screening purposes.