Cytoskeletal immunohistochemistry of Alzheimer's dementia and related diseases. A study with monoclonal antibodies.

Mabs directed against phosphorylated epitopes on the heavy and medium neurofilament protein were used to immunostain histological sections from brains of patients without neurological disease and patients suffering from SDAT, Pick's disease, Parkinson's disease, progressive supranuclear palsy and encephalomalacias of the white matter inducing chromatolysis in the overlying cortex. In normal brains only axons but never perikarya were stained. In the pathological brains, however, swollen neurons with chromatolysis and swollen cells in Pick's disease, NFT in SDAT, Pick bodies in Pick's disease, the centers of Lewy bodies in Parkinson's disease and some tangles in progressive supranuclear palsy were stained. These changes are perikaryal alterations. The results are discussed in relation to the formation of NFT in SDAT, i.e. the PHF as seen by electron microscopy. It is concluded that in spite of the reliable staining of NFT with some of our mabs, with sera directed against PHF, MAPs and other cytoskeletal proteins there is no absolutely specific immunoreaction for PHF. The most similar pattern to that observed in NFTs of SDAT is seen in the Pick bodies of Pick's disease, although these do not consist of PHF when looked at with the electron microscope, and although they behave differently from NFT in some 'conventional' histological stains. From this nonspecificity of the immunoreaction and from the presence of multiple cytoskeletal epitopes in NFT it is concluded that NFT (i.e. PHF) are probably not derived from one particular cytoskeletal element but are reassembled from proteolytic breakdown fragments of several of these elements. In this regard the similarities and dissimilarities with the alterations of Pick's disease might be specially relevant and deserve further studies, especially as the clinical features of SDAT and Pick's disease can be very similar.