Salivary Tau Species are Potential Biomarkers of Alzheimer's Disease

Article type: Research Article

Authors: Shi, Min^a | Sui, Yu-Ting^a | Peskind, Elaine R.^{b; c} | Li, Ge^b | Hwang, HyeJin^a | Devic, Ivana^a | Ginghina, Carmen^a | Edgar, John Scott^d | Pan, Catherine^a | Goodlett, David R.^d | Furay, Amy R.^{a; b} | Gonzalez-Cuyar, Luis F.^a | Zhang, Jing^{a; *}

Affiliations: [a] Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA | [b] Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA | [c] Mental Illness Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA | [d] Department of Medicinal Chemistry, University of Washington School of Pharmacy, Seattle, WA, USA

Correspondence: [*] Correspondence to: Jing Zhang, Department of Pathology, University of Washington School of Medicine, HMC Box 359635, 325 9th Ave, Seattle, WA 98104, USA. Tel.: +1 206 897 5245; Fax: +1 206 897 5452; E-mail: zhangj@uw.edu.

Abstract: 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-β 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.

Keywords: Alzheimer's disease, amyloid-β, biomarkers, saliva, tau protein

DOI: 10.3233/JAD-2011-110731

Journal: Journal of Alzheimer's Disease, vol. 27, no. 2, pp. 299-305, 2011