Tau Rather than TDP-43 Proteins are Potential Cerebrospinal Fluid Biomarkers for Frontotemporal Lobar Degeneration Subtypes: A Pilot Study
| Autor: | Joost Raaphorst, Charlotte E. Teunissen, H. Bea Kuiperij, Giuliano Binetti, Marcel M. Verbeek, Benno Küsters, Roberta Ghidoni, Marijke Beenes, Luisa Benussi, Nicolaas A. Verwey, Helenius J. Schelhaas, Anna Paterlini, Yolande A.L. Pijnenburg, Alexandra A M Versleijen |
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| Přispěvatelé: | Neurology, Laboratory Medicine, Amsterdam Neuroscience - Neurodegeneration |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Pathology medicine.medical_specialty Pilot Projects tau Proteins Disease 03 medical and health sciences 0302 clinical medicine Cerebrospinal fluid mental disorders medicine Humans Pathological Aged Aged 80 and over Immunoassay Natural course business.industry General Neuroscience Brain nutritional and metabolic diseases General Medicine Frontotemporal lobar degeneration Middle Aged Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] medicine.disease nervous system diseases DNA-Binding Proteins Psychiatry and Mental health Clinical Psychology 030104 developmental biology Homogeneous Csf biomarkers Female Geriatrics and Gerontology Frontotemporal Lobar Degeneration business 030217 neurology & neurosurgery Biomarkers Frontotemporal dementia |
| Zdroj: | Journal of Alzheimer's Disease, 55, 585-595 Kuiperij, H B, Versleijen, A A M, Beenes, M, Verwey, N A, Benussi, L, Paterlini, A, Binetti, G, Teunissen, C E, Raaphorst, J, Schelhaas, H J, Küsters, B, Pijnenburg, Y A L, Ghidoni, R & Verbeek, M M 2017, ' Tau Rather than TDP-43 Proteins are Potential Cerebrospinal Fluid Biomarkers for Frontotemporal Lobar Degeneration Subtypes : A Pilot Study ', Journal of Alzheimer's Disease, vol. 55, no. 2, pp. 585-595 . https://doi.org/10.3233/JAD-160386 ResearcherID Journal of Alzheimer's Disease, 55(2), 585-595. IOS Press Journal of Alzheimer's Disease, 55, 2, pp. 585-595 |
| ISSN: | 1387-2877 |
| Popis: | Item does not contain fulltext BACKGROUND: Frontotemporal dementia (FTD) is a heterogeneous disease both at the clinical, genetic, and pathobiological level. The underlying pathological spectrum (termed FTLD, frontotemporal lobar degeneration) is in most cases defined by accumulation of either tau (FTLD-tau) or TDP-43 proteins (FTLD-TDP). Biomarkers to differentiate these subtypes are not yet available, whereas these are essential requirements to study the natural course of disease and for homogeneous inclusion of patients in clinical studies. OBJECTIVE: To study if a combination of total (t-) and phosphorylated (p-)tau, and t-TDP-43 and p-TDP-43 proteins in cerebrospinal fluid (CSF) is suitable to discriminate FTLD-tau and FTLD-TDP subtypes. METHODS: We developed immunoassays for the quantification of t-TDP-43 and p-TDP-43 proteins and used commercially available assays for the quantification of t-tau and p-tau proteins. We quantified these proteins in ventricular CSF samples from neuropathologically defined FTLD-tau and FTLD-TDP cases to study the reflection of underlying brain pathology in CSF composition, and in lumbar CSF samples from FTLD-tau and FTLD-TDP patients to study the diagnostic potential of CSF biomarkers. RESULTS: In ventricular CSF, t-TDP-43 and t-tau levels, when combined into one model, were significantly different between neuropathologically-defined FTLD-tau and FTLD-TDP cases. In a pilot study using lumbar CSF, the p-tau/t-tau ratio, but not t-TDP-43 levels, were significantly different between FTLD-TDP and FTLD-tau patients. CONCLUSION: We conclude that with current available methods, CSF tau, rather than TDP-43 proteins, may have diagnostic value in the differentiation of FTLD patients with either tau or TDP-43 pathology. |
| Databáze: | OpenAIRE |
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