The ELISA-Measured Increase in Cerebrospinal Fluid Tau that Discriminates Alzheimer's Disease from other Neurodegenerative Disorders is not Attributable to Differential Recognition of Tau Assembly Forms

Article type: Short Communication

Authors: O'Dowd, Seán T.^{a; b} | Ardah, Mustafa T.^c | Johansson, Per^{d; e} | Lomakin, Aleksey^f | Benedek, George B.^f | Roberts, Kinley A.^b | Cummins, Gemma^b | El Agnaf, Omar M.^c | Svensson, Johan^{e; g} | Zetterberg, Henrik^h | Lynch, Timothy^b | Walsh, Dominic M.^{a; *}

Affiliations: [a] Laboratory for Neurodegenerative Research, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Republic of Ireland | [b] Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Republic of Ireland | [c] Faculty of Medicine and Health Sciences, Department of Biochemistry, United Arab Emirates University, Al Ain, United Arab Emirates | [d] Department of Neuropsychiatry, Skaraborg Hospital, Falköping, Sweden | [e] Department of Endocrinology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden | [f] Department of Physics and Center for Material Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA | [g] Department of Endocrinology, Skaraborg Hospital, Skövde, Sweden | [h] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg and Mölndal, Sweden

Correspondence: [*] Correspondence to: Dominic M. Walsh, Laboratory for Neurodegenerative Research, Center for Neurologic Diseases, Harvard Institutes of Medicine (Room 921b), 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Tel.: +1 617 5255059; Fax: +1 617 5255252; E-mail: [email protected].

Abstract: Elevated cerebrospinal fluid concentrations of tau discriminate Alzheimer's disease from other neurodegenerative conditions. The reasons for this are unclear. While commercial assay kits are widely used to determine total-tau concentrations, little is known about their ability to detect different aggregation states of tau. We demonstrate that the leading commercial enzyme-linked immunosorbent assay reliably detects aggregated and monomeric tau and evinces good recovery of both species when added into cerebrospinal fluid. Hence, the disparity between total-tau levels encountered in Alzheimer's disease and other neurodegenerative conditions is not due to differential recognition of tau assembly forms or the extent of degeneration.

Keywords: Alzheimer's disease, cerebrospinal fluid, ELISA, tau

DOI: 10.3233/JAD-2012-121393

Journal: Journal of Alzheimer's Disease, vol. 33, no. 4, pp. 923-928, 2013