Deposition of hyperphosphorylated tau (p-tau) has been observed in several neurodegenerative diseases. The six isoforms of tau are divided into two main groups including three repeat (3R) and four repeat (4R) microtubule-binding domains. Using quantitative RT-PCR method and immunohistochemistry with phosphorylation dependent anti-tau antibody (AT8), we investigated the expression level of tau mRNA isoforms in the frontal cortex and globus pallidus of patients with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) to determine whether altered expression patterns of tau mRNA isoforms correlate with p-tau accumulation. The 4R/3R ratios in frontal cortices of CBD and globus pallidus of PSP and CBD were significantly higher than the control (P<0.05). There was no correlation between the expression patterns of tau mRNA isoforms and p-tau accumulation. Our findings suggest that neurodegeneration of PSP and CBD could be regulated by alternative splicing of tau mRNA to yield high 4R/3R ratio. In addition, the lack of correlation between the expression pattern of tau mRNA isoforms and p-tau accumulation suggests that not only alternative splicing of tau mRNA, but also other factors such as post-transcriptional or translational modifications may play a role in the pathogenesis of specific neurodegeneration in PSP and CBD. (C) 2002 Elsevier Science B.V. All rights reserved.