Filamentous tau protein deposits are also the defining characteristic of other neurodegenerative diseases, many of which are frontotemporal dementias or movement disorders, such as Pick's disease, progressive supranuclear palsy and corticobasal degeneration. It is well established that the distribution of tau pathology correlates with the presence of symptoms of disease. However, until recently, there was no genetic evidence linking dysfunction of tau protein to neurodegeneration. Clinically, this condition is characterised by profound personality changes, progressive dementia and extrapyramidal symptoms. Neuropathologically, all cases with tau mutations examined to date have shown an abundant filamentous tau pathology in brain cells.
Pathological heterogeneity is determined to a large extent by the location of mutations in tau .
Known mutations are either coding region or intronic mutations located close to the splice-donor site of the intron following exon 10. Most coding region mutations produce a reduced ability of tau to interact with microtubules, thus probably setting in motion the mechanisms that lead to the formation of tau filaments. Several of these mutations also promote sulphated glycosaminoglycan-induced assembly of tau into filaments. Intronic mutations and some coding region mutations produce increased splicing in of exon 10, resulting in an overexpression of four-repeat tau isoforms. Taken together, the new work has shown that dysfunction of tau protein causes neurodegeneration and dementia.