O. Bugiani et al., Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau, J NE EXP NE, 58(6), 1999, pp. 667-677
Citations number
49
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
The tau gene has been found to be the locus of dementia with rigidity linke
d to chromosome 17. Exonic and intronic mutations have been described in a
number of families. Here we describe a P301S mutation in exon 10 of the tau
gene in a new family. Two members of this family were affected. One indivi
dual presented with frontotemporal dementia, whereas his son has corticobas
al degeneration, demonstrating that the same primary gene defect in tau can
lead to 2 distinct clinical phenotypes. Both individuals developed rapidly
progressive disease in the third decade. Neuropathologically, the father p
resented with an extensive filamentous pathology made of hyperphosphorylate
d tau protein. Biochemically, recombinant tau protein with the P301S mutati
on showed a greatly reduced ability to promote microtubule assembly.