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Tau oligomers in cerebrospinal fluid in Alzheimer's disease

Sengupta, U; Portelius, E; Hansson, O; Farmer, K; Castillo-Carranza, D; Woltjer, R; Zetterberg, H; (2017) Tau oligomers in cerebrospinal fluid in Alzheimer's disease. Annals of Clinical and Translational Neurology , 4 (4) pp. 226-235. 10.1002/acn3.382. Green open access

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Abstract

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Type: Article
Title: Tau oligomers in cerebrospinal fluid in Alzheimer's disease
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/acn3.382
Publisher version: http://dx.doi.org/10.1002/acn3.382
Language: English
Additional information: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Molecular Neuroscience
URI: http://discovery.ucl.ac.uk/id/eprint/1549750
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