βII-tubulin and phospho-tau aggregates in Alzheimer's disease and Pick's disease

The expression of beta I-, beta II- and beta III-tubulin isotypes was examined by immunohistochemistry in the entorhinal and transentorhinal cortices, hippocampus and dentate gyrus in normal human brains and in cases with Alzheimer's disease (AD), Pick's disease (PiD) and in argyrophilic grain disease (AGD). The results showed that beta II-tubulin predominated in the upper layers (mainly layer 11) and beta III-tubulin in the inner layers of the entorhinal and transentorhinal cortices in control brains.)beta II-tubulin immunoreactivity was higher than beta III-tubulin immunoreactivity in granular neurons of the dentate gyrus, whereas pyramidal neurons of the hippocampus proper were stained equally with anti-beta II-tubulin and beta III-tubulin antibodies. No preferential layering distribution was observed for beta I-tubulin. Polymerization assays with tubulin peptides following the method of microtubule-associated protein displacement demonstrated that the 01 and 0111 isotypes have a higher binding capacity for tau than does the 1311 isotype. Interestingly, about 60% of neurons with neurofibrillary tangles in layer 11 of the entorhinal and transentorhinal cortices in AD were selectively stained with anti-beta II-tubulin antibodies. Moderate beta II-tubulin immunoreactivity was also observed in Pick bodies in PiD. Taken together, these findings support the view that high beta II-tubulin content is a contributing, factor in the formation of abnormal hyper-phosphorylated tau aggregates.