Microprobe Studies of Aluminum Accumulation in Association with Human Central Nervous System Disease

The neurofibrillary tangle, first described by Alzheimer in 1907, along with the senile plaque, represent the two principle neuropathologic lesions identified in the brains of patients with Alzheimer's disease. Aluminum salts inoculated into the central nervous system of certain experimental animals induces neurofilamentous lesions which are similar, but not identical to the neurofibrillary tangles seen in Alzheimer's disease. Although some reports provide evidence of increased amounts of aluminum in the brains of Alzheimer's disease victims, such bulk analysis studies have been difficult to replicate. Over the past several years we have approached this problem using a variety of microprobe techniques in order to determine the distribution of trace elements within individual nerve cells.Using scanning electron microscopy with X-ray spectrometry, we have identified accumulations of aluminum in the neurofibrillary tangle-bearing neurons of cases of Alzheimer's disease. Similar accumulations have been found in the brains of the indigenous natives of Guam who suffer from parkinsonism with dementia and from amyotrophic lateral sclerosis. Recent studies using laser microprobe mass analysis suggest that the predominance of aluminum identified within the parikaryon of neurofibrillary tangle-bearing neurons is located within the neurofibrillary tangle itself. Although this ongoing research still cannot ascribe a causal role for aluminum in the etiology and/or pathogenesis of the neurofibrillary tangle, the data suggest that certain environmental factors related to trace elemental constituents may play an important role in the formation of this type of cellular pathology.