Distinct isoforms of tau aggregated in neurons and glial cells in brains of patients with Pick's disease, corticobasal degeneration and progressive supranuclear palsy

We investigated isoform composition of aggregated tau protein in brains wit h Pick's disease (PID), corticobasal degeneration (CBD) and progressive sup ranuclear palsy (PSP) by immunoblot analysis of sarkosyl-insoluble fraction s of brain homogenates, We also examined the adjacent brain tissues immunoh istochemically with a rabbit antibody, Ex 10, which specifically recognizes exon 10 of tan, The Ex 10 recognizes tau isoforms with four microtubule-bi nding repeats (4Rtau) but not those with three microtubule-binding repeats (3Rtau). Sarkosyl-insoluble tau from the brains of patients with CBD and PS P consisted of 4Rtau, Insoluble tau from the PiD brains contained both 3Rra u and 4Rtau, where 3Rtau predominated over 4Rtau. In brain tissues of CBD a nd PSP, Ex 10 immunostained all neuronal and glial tau-positive structures, They included pre-tangles, astrocytic plaques, tuft-shaped astrocytes, and oligodendroglial coiled bodies. In PiD brains, astrocytic inclusions were also positive for 4Rtau. However, the majority of, if not all, Pick bodies and oligodendroglial tau inclusions were negative for 4Rtau. Such results s uggest that, in neurons and oligodendroglia, tau isoforms involved in the p athological processes differ between CBD/PSP and PiD, and are thus disease specific. This contrasts with the astrocytic tau isoforms that accumulate s imilarly in all three disorders.