Salivary Tau Species are Potential Biomarkers of Alzheimer's Disease

Abstract

Phosphorylation of tau protein is a critical event in the pathogenesis of Alzheimer disease (AD). Increased phosphorylated tau and total tau levels, combined with reduced concentrations of amyloid beta 1–42 (Aβ42) 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 Aβ 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 Aβ42 using highly sensitive Luminex assays revealed that, while Aβ42 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.

Activity-dependent neuroprotector homeobox protein: A candidate protein identified in serum as diagnostic biomarker for Alzheimer's disease

“…Previous studies have also indicated some candidate screening biomarkers for AD such as tau and phosphorylated tau in saliva [8], and α-2-macroglobulin, amyloid, and apolipoproteins in serum [9][10][11]. The most reproducible findings were decreased expression of β-amyloid 1-42 and increased expression of tau and phospho-tau (ptau-181) in CSF samples [6,8,[12][13][14]. However, obtaining CSF for clinical diagnosis in the early stage of AD is challenging.…”

“…It is important to develop a reliable and accurate clinical blood test method for AD. In previous studies, blood-or serum-based biomarkers for the detection of AD were reported [7][8][9][10][11]14,16]. Blood-based biomarkers are possible and plausible, but more work has to be done to carefully examine the design of studies, the collection and accessibility of cohorts and samples, and the use of technologies [7].…”

Saliva diagnostics – Current views and directions

“…Salivary diagnostics is also used in some neurodegenerative diseases like Alzheimer's disease, where Shi et al 122 found elevated levels of phosphorilated and total TAU proteins compared to healthy individuals.…”

The Human Salivary Proteome is Radiation Responsive

“…Recent work has also focused on the discovery of salivary biomarkers of brain injury and disease. For example, tau proteins, which are microtubule-stabilizing proteins found in neurons of the central nervous system, have been found in saliva and phosphorylated tau/total tau protein ratios are significantly increased in patients with Alzheimer's disease (17). Two important potential biomarkers of Parkinson's disease, α-synuclein (α-Syn) and DJ-1, have also been detected in saliva (18).…”