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A novel tau mutation in exon 9 (1260V) causes a four-repeat tauopathy

Grover, A; England, E; Baker, M; Sahara, N; Adamson, J; Granger, B; Houlden, H; Passant, Ulla LU ; Yen, SH and DeTure, M, et al. (2003) In Experimental Neurology 184(1). p.131-140
Abstract
A novel mutation in exon 9 of tau, I260V, is associated with a clinical syndrome consistent with frontotemporal dementia with extensive tau pathology; however, neurofibrillary tangles and Pick bodies are absent. Significantly, Sarkosyl- insoluble tau extracted from affected brain tissue consisted almost exclusively of four-repeat isoforms. Consistent with these findings, in vitro biochemical assays demonstrated that the I260V mutation causes a selective increase in tau aggregation and a decrease in tau-induced microtubule assembly with four-repeat isoforms only. The contrasting pathology and biochemical effects of this mutation suggest a different disease mechanism from the other exon 9 mutations and demonstrates the critical role for the... (More)
A novel mutation in exon 9 of tau, I260V, is associated with a clinical syndrome consistent with frontotemporal dementia with extensive tau pathology; however, neurofibrillary tangles and Pick bodies are absent. Significantly, Sarkosyl- insoluble tau extracted from affected brain tissue consisted almost exclusively of four-repeat isoforms. Consistent with these findings, in vitro biochemical assays demonstrated that the I260V mutation causes a selective increase in tau aggregation and a decrease in tau-induced microtubule assembly with four-repeat isoforms only. The contrasting pathology and biochemical effects of this mutation suggest a different disease mechanism from the other exon 9 mutations and demonstrates the critical role for the first microtubule-binding domain in tau-promoted microtubule assembly and the pathogenic aggregation of tau. (Less)
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Contribution to journal
publication status
published
subject
keywords
neurodegeneration, dementia, pick body, glial tau, axonal, microtubule assembly, aggregation, isoform, tau, four-repeat
in
Experimental Neurology
volume
184
issue
1
pages
131 - 140
publisher
Academic Press
external identifiers
  • wos:000186804800018
  • pmid:14637086
  • scopus:0345689371
ISSN
0014-4886
DOI
10.1016/S0014-4886(03)00393-5
language
English
LU publication?
yes
id
1d358115-738c-4f46-8cd3-ac69e2daf211 (old id 294573)
date added to LUP
2007-08-02 15:50:50
date last changed
2018-10-03 10:50:22
@article{1d358115-738c-4f46-8cd3-ac69e2daf211,
  abstract     = {A novel mutation in exon 9 of tau, I260V, is associated with a clinical syndrome consistent with frontotemporal dementia with extensive tau pathology; however, neurofibrillary tangles and Pick bodies are absent. Significantly, Sarkosyl- insoluble tau extracted from affected brain tissue consisted almost exclusively of four-repeat isoforms. Consistent with these findings, in vitro biochemical assays demonstrated that the I260V mutation causes a selective increase in tau aggregation and a decrease in tau-induced microtubule assembly with four-repeat isoforms only. The contrasting pathology and biochemical effects of this mutation suggest a different disease mechanism from the other exon 9 mutations and demonstrates the critical role for the first microtubule-binding domain in tau-promoted microtubule assembly and the pathogenic aggregation of tau.},
  author       = {Grover, A and England, E and Baker, M and Sahara, N and Adamson, J and Granger, B and Houlden, H and Passant, Ulla and Yen, SH and DeTure, M and Hutton, M},
  issn         = {0014-4886},
  keyword      = {neurodegeneration,dementia,pick body,glial tau,axonal,microtubule assembly,aggregation,isoform,tau,four-repeat},
  language     = {eng},
  number       = {1},
  pages        = {131--140},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {A novel tau mutation in exon 9 (1260V) causes a four-repeat tauopathy},
  url          = {http://dx.doi.org/10.1016/S0014-4886(03)00393-5},
  volume       = {184},
  year         = {2003},
}