Alterations in human tau transcripts correlate with those of neurofilament in sporadic tauopathies.

Abnormalities in tau mRNA splicing cause frontotemporal dementia and parkinsonism linked to chromosome 17, and similar alterations are suggested in sporadic tauopathies such as progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). We have analyzed the expression of three-repeat (3R) and four-repeat (4R) tau isoforms in brains with familial and sporadic tauopathies. By RT-PCR analysis, decreased levels of 3R tau mRNA were detected not only in severely affected cases with progressive supranuclear palsy or corticobasal degeneration but also in cases with Alzheimer's disease or Pick's disease. Levels of 3R tau transcripts were closely correlated with levels of neurofilament transcripts. By contrast, expressions of glial fibrillary acidic protein and myelin basic protein were similar in all brains. These results suggest that decrease of 3R tau mRNA associated with loss of neuronal element may largely contribute to the increased ratio of 4R/3R tau mRNA in sporadic tauopathies.