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.
Original language | English (US) |
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Pages (from-to) | 131-140 |
Number of pages | 10 |
Journal | Experimental Neurology |
Volume | 184 |
Issue number | 1 |
DOIs | |
State | Published - Nov 2003 |
Keywords
- Aggregation
- Axonal
- Dementia
- Four-repeat
- Glial tau
- Isoform
- Microtubule assembly
- Neurodegeneration
- Pick body
- Tau
ASJC Scopus subject areas
- Neurology
- Developmental Neuroscience