PHOSPHORYLATION OF SPECIFIC SETS OF TAU-ISOFORM REFLECTS DIFFERENT NEUROFIBRILLARY DEGENERATION PROCESSES

Tau proteins are the basic components of filaments that accumulate wit hin neurons during neurofibrillary degeneration, a degenerating proces s with disease-specific phenotypes. This specificity is likely to be s ustained by both phosphorylation state and isoform content of tau aggr egates that form neuronal inclusions. In the present study, characteri zation of tau isoforms involved in neurofibrillary degeneration in Alz heimer's disease, Pick's disease, corticobasal degeneration and progre ssive supranuclear palsy was performed, Both analyses by immunoblottin g using specific tau antibodies and cell transfection by tau isoform c DNAs allowed us to demonstrate the aggregation of (1) the six hyperpho sphorylated tau isoforms in Alzheimer's disease, (2) tau isoforms with out exon 10-encoding sequence in Pick's disease and (3) hyperphosphory lated exon 10-tau isoforms in corticobasal degeneration and progressiv e supranuclear palsy. Thus, neurofibrillary degeneration phenotypes ar e likely to be related to the phosphorylation of different combination s of tau isoforms (with and/or without exon 10-encoding sequence) in s ubpopulations of neurons. (C) 1998 Federation of European Biochemical Societies.