The etiology and pathogenesis of Alzheimer's disease (AD) remains unknown. Although important advances have been made in the past year and a half towards characterizing molecular genetic processes which may underlie the development of this disorder, it is likely that a combination of both genetic and environmental factors is involved. A potential environmental factor implicated in the pathogenesis of AD is the neurotoxicity of aluminum. For the past ten years our laboratory has provided the principal scientific data upon which aluminum is linked, to the pathogenesis of AD. Using tissue microprobe approaches, we have demonstrated the presence of selective accumulation of aluminum in neurofibrillary tangle-bearing neurons, a major neuropathologic feature of AD. In the proposed study we will evaluate whether aluminum accumulation is confined solely to the neurofibrillary tangle-bearing neurons or whether trace elemental abnormalities are encountered in association with the other forms of cytopathology seen in the brains of AD victims, namely senile plaques, granulovacuolar degeneration, Hirano bodies, and vascular amyloid deposition. For this study we will employ laser microprobe mass analysis, an extremely sensitive arid precise technique for defining trace elemental content and distribution within tissue specimens. We will, in addition, investigate the nature of the aluminum accumulations seen in association with neurofibrillary tangles by evaluating the trace elemental content of extracellular """"""""ghost"""""""" tangles and a hippocampal cell population resistant to neurofibrillary tangle formation, namely the neurons of the H2 region. By studying non-CNS organs known to accumulate aluminum, we will evaluate if excessive systemic aluminum exposure to the element has occurred. By expanding our knowledge of the composition, location and association of these trace elemental abnormalities with the various forms of cytopathology seen in AD we can begin to appreciate their nature and consequences.
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