title: Salivary tau species are potential biomarkers of Alzheimer's disease.
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.
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Sui
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Peskind
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: HyeJin
authors.initials: H
authors.lastname: Hwang
authors.forename: Ivana
authors.initials: I
authors.lastname: Devic
authors.forename: Carmen
authors.initials: C
authors.lastname: Ginghina
authors.forename: John Scott
authors.initials: JS
authors.lastname: Edgar
authors.forename: Catherine
authors.initials: C
authors.lastname: Pan
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
authors.forename: Amy R
authors.initials: AR
authors.lastname: Furay
authors.forename: Luis F
authors.initials: LF
authors.lastname: Gonzalez-Cuyar
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism*; D000595:Amino Acid Sequence; D015415:Biomarkers / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D008969:Molecular Sequence Data; D010865:Pilot Projects; D012471:Salivary Proteins and Peptides / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D012471:Salivary Proteins and Peptides; D016875:tau Proteins