Different distribution of phosphorylated tau protein isoforms in Alzheimer's and Pick's diseases.

Tau proteins aggregate into different neuronal inclusions in several neurodegenerative disorders. In Alzheimer's disease (AD), hyperphosphorylated Tau from paired helical filaments (PHF) of neurofibrillary tangles, named PHF-Tau, have an electrophoretic profile with four main bands (Tau 55, 64, 69, 74 kDa). In Pick's disease, phosphorylated Tau from Pick bodies are made of two major components (Tau 55, 64 kDa) and a minor 69 kDa. Here we show, using specific antibodies against translated exon 2, 3 or 10 of Tau isoforms, that the set of Tau isoforms engaged in the most insoluble part of PHF in AD is made of Tau isoforms with exon 10 while they are lacking in phosphorylated Tau from Pick's disease. Our results suggest that specific sets of Tau isoforms distinguish between typical neuronal inclusions.