Sequestration of tubulin in neurons in Alzheimer's disease

In Alzheimer's disease (AD), a variety of populations of neurons exhibits cytoskeletal abnormalities, including neurofibrillary tangles (NFT) in perikarya, Hirano bodies in dendrites and filament-distended axons/terminals/dendrites (neurites) in senile plaques. Some nerve cells, particularly pyramidal neurons of the hippocampus, also develop Hirano bodies (paracrystalline arrays of actin) and granulovacuolar degeneration (GVD; granular inclusions in cytoplasmic vacuoles). Since abnormalities of cytoskeletal elements have been implicated in the formation of NFT, neurites and Hirano bodies, the present study was designed to determine whether GVD also may represent a type of cytoskeletal pathology. Sections of hippocampus from controls and from individuals with AD were stained by immunocytochemical methods using monoclonal and polyclonal antibodies directed against a variety of cytoskeletal antigens. Granules of GVD contained tubulin-like immunoreactivity and absorption with purified tubulin abolished staining. Other antigens were not demonstrated in granules when antibodies directed against other cytoskeletal antigens were used. The observation of sequestration of tubulin in granules is consistent with the concept that abnormalities of the neuronal cytoskeleton are an important part of the cellular pathology of AD.