[Visualization of tau isoforms by splicing-site specific antibodies]

Abstract

We have developed five tau antibodies that recognize each of 6 human tau isoforms to examine tau lesions such as Alzheimer's neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) as well as other tauopachies. These five antibodies were designed to be specific to splicing-sites of exon 2, exon 3, or exon10 or to the amino acid sequence in exon 3 or exon10. All of newly prepared antibodies as well as anti-human tau stained corresponding recombinant tau isoforms and isolated hyperphosphorylated tau isoforms in an isoform-specific manner on western blot. All antibodies were also found to decorate immunohistochemically NFTs but to be present in unequal amounts in NFTs where two tau isoforms (tau1-352 and tau1-381) were the major species. It is not easy to compare immunoreaction based on immunohistochemical analysis with multiple antibodies. However, the present result strongly suggest unequal occurrence of tau isoforms in Alzheimer's NFTs, indicating other isoform selection in AD than tauopathies.