Filaments of Pick's bodies contain altered cytoskeletal elements

Abstract

Pick's disease, a form of progressive senile dementia, is distinguished by the presence of neuronal inclusions known as Pick's bodies. The Pick's body consists mostly of sparse 10-20-nm straight filaments admixed with other cytoplasmic elements. This ultrastructural study was undertaken to establish which components of the Pick's body share epitopes with the normal neuronal cytoskeleton and with Alzheimer's paired helical filaments. Vibratome sections from postmortem brains of patients afflicted with Pick's disease were immunostained by means of polyclonal and monoclonal antibodies to neurofilaments, an antiserum to microtubule proteins not cross-reacting with neurofilaments, and an antiserum to Alzheimer's paired helical filaments. All the antibodies have been shown previously to react with Alzheimer's paired helical filaments. The peroxidase-antiperoxidase or indirect immunogold procedure was used for immunostaining. In addition, we used Bodian's silver stain, which has a high affinity for neurofilaments. At the electron-microscopic level the antibodies and Bodian's silver reacted with the straight filaments and some amorphous elements contained within the Pick's body. The following preadsorptions blocked the immunoreaction: neurofilament antibodies with neurofilaments; microtubule antibodies with microtubule protein or a preparation of the microtubule associate protein, tau; antibodies to paired helical filaments with Alzheimer's brain tissue. Treatment of brain tissue containing Pick's bodies with sodium dodecyl sulfate, a solvent of the normal neuronal cytoskeleton, did not dissolve straight 12-nm filaments. The detergent extracted filaments contained the same isotopes as the Pick's filaments in intact tissue. These results demonstrate that the straight filament components of the Pick's body contain the same neurofilament and microtubule epitopes as the Alzheimer's paired helical filaments and that the filaments share insolubility characteristics similar to those of the paired helical filaments. It is proposed that these two structures are related and are derived at least in part from altered components of the normal neuronal cytoskeleton.