Distribution of isoforms of the microtubule-associated protein tau in grey and white matter areas of human brain: A two-dimensional gelelectrophoretic analysis

The microtubule-associated protein tan in human brain consists of six molecular isoforms derived from a single gene by alternative mRNA-splicing and further modified by posttranslational processing. In the present study, the distribution of tan isoforms in grey and white matter of human temporal cortex was investigated by two-dimensional gelelectrophoresis. More than 80 isoforms were defected. The pattern of isoforms obtained after treatment with alkaline phosphatase was still more complex than those of recombinant tau, indicating that posttranslational modifications other than phosphorylation contribute to the molecular heterogeneity of tan. The tau isoform D according to Goedert [1] containing four tubulin-binding regions shown to promote tubulin polymerisation most efficiently was present in higher amounts in white as compared to grey matter. The pattern of isoform distribution was not significantly altered in Alzheimer's disease. It is concluded that molecular isoforms that differ in their tubulin-binding characteristics are differentially distributed in subcellular neuronal compartments and/or neuronal types.