A double-labeling immunohistochemical study of tau exon 10 in Alzheimer's disease, progressive supranuclear palsy and Pick's disease

Neurofibrillary tangles (NFT), one of the histopathological hallmarks of Al zheimer's disease (AD) and progressive supranuclear palsy (PSP), and Pick b odies in Pick's disease (PiD) are composed of microtubule-associated protei n tau, which is the product of alternative splicing of a gene on chromosome 17. Alternative expression of exon 10 leads to formation of three- or four -repeat tau isoforms. To study the differential expression of exon 10, we p erformed double-labeling immunohistochemistry of the hippocampal formation in nine AD, four PSP and three PiD cases. Cryostat sections were processed with and without formic acid (FA) treatment, and double-stained with anti-t au (Alz-50 or PHF-1) or anti-amyloid P component antibodies and one of two specific anti-exon 10 antibodies (E-10). The effect of proteinase-K treatme nt was also evaluated. The results suggest the following. First. in AD, E-1 0 immunoreactivity is present in most intracellular NFT, but not in most dy strophic neurites and neuropil threads, suggesting differential expression of tau isoforms in specific cellular domains. Second, in AD, E-10 immunorea ctivity is lost or blocked in most extracellular NFT, possibly due to prote olysis. Third, in PSP, E-10 immunoreactivity is hidden or blocked in NFT an d tau-positive glial inclusions, but FA treatment exposes the epitope consi stent with the hypothesis that PSP inclusions contain four-repeat tau. Four th, E-10 immunoreactivity is present in dentate fascia NFT in AD and PSP, b ut not in Pick bodies in the dentate fascia or other areas. The results sug gest that expression of exon 10 in tau is specific for cellular domains in a disease-specific manner.