Neuronal cytoskeleton is composed of microfilaments, neurofilaments and microtubules which show distinctive ultrastructural characteristics. Different groups of antibodies against neurofilaments and microtubule associated proteins which were grouped according to their specificity for proteins of perykarium, axons and/or dendrites have been produced. A 8.6 kD polypeptide called ubiquitin has been recognized as one of the heat shock proteins. Ubiquitin is implicated in the non-lysosomal degradation of abnormal proteins and other proteolytic intracellular mechanisms. Several immunohistological studies on Alzheimer's disease (AD)-neurofibrillary tangles (NFTs) demonstrated that antibodies for different normal cytoskeletal components bind to NFTs-bearing neurons. AD-NFTs could be also demonstrated using antibodies for the beta-amyloid protein. The production and accumulation of abnormal proteins such as those observed in AD-NFTs induce a ubiquitin-mediated degradative pathway to remove them. It has been demonstrated that ubiquitin is covalently associated with insoluble neurofibrillary material of AD-NFTs. Topographical differences in the distribution of NFTs underscore that different neuronal populations including neocortical neurones are affected in progressive supranuclear palsy (PSP) and AD. Differences in the molecular composition of PSP-NFTs highlighted by immunochemical studies induce us to speculate that different physio- and aetiopathogenetic mechanisms are operative in the production of PSP-NFTs.