This project is aimed at understanding the biology and molecular pathogenesis of aging in the nervous system. Alzehimer's disease is the most common organic dementia seen in old age. In this disease an important histopathological lesion is the presence of neurofibrillary tangles which contain mostly paired helical filaments. Antibodies raised against several normal neurofibrous proteins have been used to study the molecular nature of tangles. Information available indicates that tangles share antigenic determinants with neurofilament protein and vimentin. It is unknown if additional elements are involved in making tangles. Recently by immunization of mice with a partially purified tangle fraction and subsequent hybridization of an immunized mouse spleen cells with myeloma cells, we produced a monoclonal anti-tangle antibody. This antibody does not recognize neurofilament in axons or vimentin in HeLa cells but bind to HeLa cell nuclei and mitotic spindle. The identity of this tangle-related antigen and the function of the antigen in cell division will be one of the subjects of our continuing studies. In addition, we proposed to immunize more mice with partially purified neurofibrillary tangles and raise a panel of monoclonal antibodies against different determinants of the tangles. These antibodies will be used to determine if tangles contain pathologic specific components or additional normal brain components, to provide further evidence that tangles and neurofilament proteins and vimentin have common immunological properties and to further purify tangles. A separate project funded previously concerns the distribution of brain glial filament protein (GFP) in the peripheral nervous system (PNS). We have demonstrated that in PNS the GFP is distributed primarily in Schwann cells associated with unmyelinated axons and that the GFP of CNS and PNS have common biochemical properties. In continuing studies, we propose to determine if axons dictate the expression of GFP in Schwann cells. We will use ultrastructural, immunohistochemical and biochemical techniques to examine isolated nerve stumps, cross-anastomosed myelinated and unmyelinated nerves of adult rats.
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