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Ann Clin Transl Neurol. 2017 Mar 1;4(4):226-235. doi: 10.1002/acn3.382. eCollection 2017 Apr.

Tau oligomers in cerebrospinal fluid in Alzheimer's disease.

Author information

Mitchell Center for Neurodegenerative DiseasesUniversity of Texas Medical BranchGalvestonTexas; Department of Neurology, and Neuroscience and Cell BiologyUniversity of Texas Medical BranchGalvestonTexas.
Clinical Neurochemistry Laboratory Institute of Neuroscience and Physiology the Sahlgrenska Academy at University of Gothenburg Mölndal Sweden.
Clinical Memory Research UnitDepartment of Clinical SciencesLund UniversityLundSweden; Memory ClinicSkåne University HospitalLund Sweden.
Department of Department of Pathology Oregon Health & Science University Portland Oregon.
Clinical Neurochemistry LaboratoryInstitute of Neuroscience and Physiologythe Sahlgrenska Academy at University of GothenburgMölndalSweden; Department of Molecular NeuroscienceUCL Institute of NeurologyQueen SquareLondonWC1N 3BGUnited Kingdom.
Department of Neuroscience University of California San Diego San Diago California.



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.

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