Salivary Tau Species are Potential Biomarkers of Alzheimer's Disease

Phosphorylation of tau protein is a critical event in the pathogenesis of Alzheimer's disease (AD). Increased phosphorylated tau and total tau levels, combined with reduced concentrations of amyloid-beta 1-42 (A beta(42)) in cerebrospinal fluid (CSF), but not in plasma or serum, have been generally accepted as sensitive AD diagnostic markers. However, obtaining CSF is a relatively invasive procedure that requires participation of specially trained medical professionals, i.e., CSF is not an ideal sample source for screening or early diagnosis of AD, which is essential to current and future neuroprotective treatments for the disease. Here, we identified tau, but not A beta species, with mass spectrometry in human saliva, a body fluid that is much more accessible compared to CSF or even blood. Quantitative assessment of salivary levels of total tau, phosphorylated tau, and A beta(42) using highly sensitive Luminex assays revealed that, while A beta(42) was not detectable, the phosphorylated tau/tau ratio significantly increased in patients with AD compared to healthy controls. These results suggest that salivary tau species could be ideal biomarkers for AD diagnosis, especially at early stages of the disease or even screening asymptomatic subjects, allowing for a much larger therapeutic window for AD patients.