No abstract

To investigate the extent to which whole tau proteins, structurally abnormal tau and fragments of tau are incorporated into neurofibrillary tangles in Alzheimer's disease, an immunocytochemical mapping study using a panel of antibodies to several synthetic human tau peptides has been performed. Neurofibrillary tangles were immunolabelled in situ, and paired helical filaments (PHF), the principal structural component of tangles, were immunolabelled after isolation and Pronase treatment. N-Terminal and C-terminal domains of tau were found to be present in tangles in situ. SDS-treated PHF were found to contain most of the C-terminal half of tau and were also labelled by antibodies to ubiquitin. Only some of these PHF were labelled by antisera to tau sequences towards the N-terminus, and this enabled the identification of a region of tau in which proteolytic cleavage may occur. The ultrastructural appearance of the immunolabelling suggested that both the N-and C-terminal domains of tau extend outwards from the axis of PHF. After Pronase treatment, PHF were strongly labelled only by an antiserum to PHF and by the antiserum to the most C-terminal tau synthetic peptide. The latter antiserum also strongly labelled extracellular tangles in situ, whereas these extracellular tangles were poorly labelled by the antisera to the other synthetic peptides. One anti-(tau peptide) serum labelled a population of neurofibrillary tangles in situ only after alkaline phosphatase pretreatment of tissue sections. Our results show that, although peptides along the length of the tau molecule are associated with neurofibrillary tangles in situ, only the C-terminal one-third of the molecule is tightly associated with PHF, since this region of tau is resistant to SDS treatment of PHF. We also report the existence in PHF in situ of a masked tau epitope which is partially unmasked by dephosphorylation. These results are indicative of post-translational changes in tangle-associated tau in degenerating neurons in Alzheimer's disease.

Several antibodies directed against the heterogeneous microtubule-associated protein group tau have been used to determine the immunocytochemical localization of these proteins in the developing rat cerebellum. Immunoblot analysis of brain extracts showed that both monoclonal and polyclonal anti-tau antibodies revealed not only the adult tau proteins (50,000-70,000 mol. wt) but also the immature (48,000 mol. wt) tau form. Immunocytochemical studies showed that, whatever the stage of development, anti-tau antibodies stained several types of axonal fibres. The Purkinje cell bodies and their dendrites were never significantly labelled. This means that immature tau is, as adult tau, localized essentially in axons. Axonal labelling seems to follow the cerebellar developmental pattern. For instance, the climbing fibres which reach the cerebellum during the embryonic life were stained soon after birth by the anti-tau antibodies. In contrast, the parallel fibres, that begin to develop perinatally, do not express tau at early (5 days) postnatal stages; a clear labelling of the deeper parallel fibres (which are more mature than the superficial ones) was seen at day 10 after birth in the vicinity of the developing dendrites of the Purkinje cells. This suggests that (1) the appearance of tau immunoreactivity reflects a certain stage of maturity of the parallel fibre; (2) both immature and mature tau microtubule-associated proteins seem to be axon specific in the developing rat cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS)

Between January 1984 and December 1990. 65 intramedullary spinal cord tumors were diagnosed and operated on. In this series, all patients underwent magnetic resonance imaging investigations and were operated on with the Cavitron ultrasonic surgical aspirator whenever necessary. Major surgical difficulties have been found in patients previously treated by radiotherapy with or without biopsy. We found magnetic resonance imaging to be a highly sensitive imaging procedure and the method of choice for visualizing tumors within the spinal cord. Nevertheless, accurate diagnosis may only be suggested by magnetic resonance imaging, rather than made definitively. Surgery is necessary in every case in order to obtain a definite diagnosis. Radical surgery can be performed when a plane exists between the tumor and the normal spinal cord: biopsy or debulking with the Cavitron ultrasonic surgical aspirator should be performed when the tumor is infiltrative. We have performed 33 so-called total resections, 22 partial resections, and 10 biopsies, among which 5 were performed on lipomas. Surgical results were assessed at 3 months after surgery, showing 35 improvements (53%), 24 stabilizations (37%), and 6 deteriorations (10%).