Microanalysis of senile plaques using nuclear microscopy

Silver-staining "senile" plaques occurring in the brain are a major part of the pathology of Alzheimer's disease. The elemental composition of these structures, and the possible presence of aluminum and silicon in these structures, has been the subject of an increasing research effort over the last decade. However, the results have often been contradictory. Using a scanning proton microprobe, the elemental composition of senile plaques has been determined. This instrument, similar to an electron probe, uses a focused beam of protons scanned across a sample to map the elements. The technique is absolutely quantitative and is sensitive down to the parts per million level. Tissue from six cases of clinically and pathologically characterized cases of Alzheimer's disease and two aged neurologically normal controls was scanned. It was found that aluminum and silicon occur at a level of 50 ppm or greater in the cores of 20% of senile plaques and that the total occurrence of aluminum or silicon in scans containing plaques was not above background. The major uncertainties affecting interpretation of results of this kind are discussed, and it is suggested that the least controllable factor is contamination in the reagents used to prepare and stain the tissue. This indicates that until plaques can be unambiguously identified and analyzed in untreated tissue, no conclusion can be reached on whether senile plaques contain aluminum and silicon.