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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The L266V tau mutation is associated with frontotemporal dementia and Pick-like 3R and 4R tauopathy.

We report a case of rapidly progressive frontotemporal dementia presenting at age 33 years. At autopsy there was severe atrophy of the frontal and temporal lobes. Tau-positive Pick bodies, which ultrastructurally were composed of straight filaments, were present, accompanied by severe neuronal loss and gliosis. RD3, a tau antibody specific for the three-repeat (3R) isoforms, labeled the Pick bodies. ET3, a four-repeat (4R) isoform-specific tau antibody, did not label Pick bodies, but highlighted rare astrocytes, and threads in white matter bundles in the corpus striatum. Analysis of the tau gene revealed an L266V mutation in exon 9. Analysis of brain tissue from this case revealed elevated levels of exon 10+ tau RNA and soluble 4R tau. However, both 3R and 4R isoforms were present in sarkosyl-insoluble tau fractions with a predominance of the shortest 3R isoform. The L266V mutation is associated with decreased rate and extent of tau-induced microtubule assembly, and a 3R isoform-specific increase in tau self assembly as measured by an in vitro assay. Combined, these data indicate that L266V is a pathogenic tau mutation that is associated with Pick-like pathology. In addition, the results of the RD3 and ET3 immunostains clearly explain for the first time the presence of both 3R and 4R tau isoforms in preparations of insoluble tau from some Pick's disease cases.[1]


  1. The L266V tau mutation is associated with frontotemporal dementia and Pick-like 3R and 4R tauopathy. Hogg, M., Grujic, Z.M., Baker, M., Demirci, S., Guillozet, A.L., Sweet, A.P., Herzog, L.L., Weintraub, S., Mesulam, M.M., LaPointe, N.E., Gamblin, T.C., Berry, R.W., Binder, L.I., de Silva, R., Lees, A., Espinoza, M., Davies, P., Grover, A., Sahara, N., Ishizawa, T., Dickson, D., Yen, S.H., Hutton, M., Bigio, E.H. Acta Neuropathol. (2003) [Pubmed]
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