Pathological inclusion bodies in tauopathies contain distinct complements of tau with three or four microtubule-binding repeat domains as demonstrated by new specific monoclonal antibodies
| Autor: | Andrew D. Hope, Rina Bandopadhyay, Andrew J. Lees, R de Silva, G M Gibb, Brian H. Anderton, C Strand, T Jowett, T Revesz, Nicola Wood, Nadeem A. Khan, Tammaryn Lashley, Diane P. Hanger, JL Holton, Andrew R. Reid, Michelle A. Utton |
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| Rok vydání: | 2003 |
| Předmět: |
Gene isoform
Genetics Pathology medicine.medical_specialty Histology biology Tau protein Neurodegeneration medicine.disease Inclusion bodies Pathology and Forensic Medicine Progressive supranuclear palsy Exon Neurology Physiology (medical) biology.protein medicine Corticobasal degeneration Neurology (clinical) Frontotemporal dementia |
| Zdroj: | Neuropathology and Applied Neurobiology. 29:288-302 |
| ISSN: | 0305-1846 |
| Popis: | Pathological inclusions containing fibrillar aggregates of hyperphosphorylated tau protein are a characteristic feature in the tauopathies, which include Alzheimer's disease, frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), progressive supranuclear palsy, corticobasal degeneration and Pick's disease. Tau isoform composition and cellular and regional distribution as well as morphology of these inclusions vary in each disorder. Recently, several pathological missense and exon 10 splice-donor site mutations of the tau gene were iden-tified in FTDP-17. Exon 10 codes for the second of four microtubule-binding repeat domains. The splice-site mutations result in increased inclusion of exon 10 which causes a relative increase in tau isoforms containing four microtubule-binding repeat domains over those containing three repeat domains. This could be a central aetiological mechanism in FTDP-17 and, perhaps, other related tauopathies. We have investigated changes in the ratio and distribution of three-repeat and four-repeat tau in the different tauopathies as a basis of the phenotypic range of these disorders and the selective vulnerability of different subsets of neurones. In this study, we have developed two monoclonal antibodies, RD3 and RD4 that effectively distinguish these closely related tau isoforms. These new isoform-specific antibodies are useful tools for analysing tau isoform expression and distribution as well as pathological changes in the human brain. |
| Databáze: | OpenAIRE |
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