title: Tau oligomers in cerebrospinal fluid in Alzheimer's disease.
abstract: With an increasing incidence of Alzheimer's disease (AD) and neurodegenerative tauopathies, there is an urgent need to develop reliable biomarkers for the diagnosis and monitoring of the disease, such as the recently discovered toxic tau oligomers. Here, we aimed to demonstrate the presence of tau oligomers in the cerebrospinal fluid (CSF) of patients with cognitive deficits, and to determine whether tau oligomers could serve as a potential biomarker for AD.
  
  
  
  A multicentric collaborative study involving a double-blinded analysis with a total of 98 subjects with moderate to severe AD (N= 41), mild AD (N= 31), and nondemented control subjects (N= 26), and two pilot studies of 33 total patients with AD (N= 19) and control (N= 14) subjects were performed. We carried out biochemical assays to measure oligomeric tau from CSF of these patients with various degrees of cognitive impairment as well as cognitively normal controls.
  
  
  
  Using a highly reproducible indirect ELISA method, we found elevated levels of tau oligomers in AD patients compared to age-matched controls. Western blot analysis confirmed the presence of oligomeric forms of tau in CSF. In addition, the ratio of oligomeric to total tau increased in the order: moderate to severe AD, mild AD, and controls.
  
  
  
  These assays are suitable for the analysis of human CSF samples. These results here suggest that CSF tau oligomer measurements could be optimized and added to the panel of CSF biomarkers for the accurate and early detection of AD.
authors.affiliation: Mitchell Center for Neurodegenerative Diseases University of Texas Medical Branch Galveston Texas; Department of Neurology, and Neuroscience and Cell Biology University of Texas Medical Branch Galveston Texas.
authors.forename: Urmi
authors.initials: U
authors.lastname: Sengupta
authors.affiliation: Clinical Neurochemistry Laboratory Institute of Neuroscience and Physiology the Sahlgrenska Academy at University of Gothenburg Mölndal Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Portelius
authors.affiliation: Clinical Memory Research Unit Department of Clinical Sciences Lund University Lund Sweden; Memory Clinic Skåne University HospitalLund Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
authors.affiliation: Mitchell Center for Neurodegenerative Diseases University of Texas Medical Branch Galveston Texas; Department of Neurology, and Neuroscience and Cell Biology University of Texas Medical Branch Galveston Texas.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Farmer
authors.affiliation: Mitchell Center for Neurodegenerative Diseases University of Texas Medical Branch Galveston Texas; Department of Neurology, and Neuroscience and Cell Biology University of Texas Medical Branch Galveston Texas.
authors.forename: Diana
authors.initials: D
authors.lastname: Castillo-Carranza
authors.affiliation: Department of Department of Pathology Oregon Health & Science University Portland Oregon.
authors.forename: Randall
authors.initials: R
authors.lastname: Woltjer
authors.affiliation: Clinical Neurochemistry Laboratory Institute of Neuroscience and Physiology the Sahlgrenska Academy at University of Gothenburg Mölndal Sweden; Department of Molecular Neuroscience UCL Institute of Neurology Queen Square London WC1N 3BG United Kingdom.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Neuroscience University of California San Diego San Diago California.
authors.forename: Douglas
authors.initials: D
authors.lastname: Galasko
authors.affiliation: Clinical Neurochemistry Laboratory Institute of Neuroscience and Physiology the Sahlgrenska Academy at University of Gothenburg Mölndal Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Mitchell Center for Neurodegenerative Diseases University of Texas Medical Branch Galveston Texas; Department of Neurology, and Neuroscience and Cell Biology University of Texas Medical Branch Galveston Texas.
authors.forename: Rakez
authors.initials: R
authors.lastname: Kayed