The role of aluminum in the etiology of Alzheimer's disease remains controversial because of the contradictory results of the many measurements of Alzheimer's brain specimens by methods including electron-probe x-ray microanalysis (EPMA), proton-induced x-ray emission (PIXE), secondary ion mass spectrometry (SIMS), and laser microprobe mass analysis (LAMMA). For many of these measurements, fixatives and stains were relied upon to facilitate the unambiguous identification of plaques and neurofibrillary tangles (NFTs), the indicators of the disease. However, the chemical processes of fixing and staining compromise the distributions and concentrations of aluminum and other elements of interest. Measurements on unfixed, unstained sections in which elemental distributions are assumed to be preserved are questioned because the identification of the structures being measured is difficult. A methodology which permits the unambiguous identification of plaques and NFTs, does not alter the elemental distributions, and provides detectibility and rapid imaging of the aluminum distribution at concentrations in the ppm range is being developed. The methodology utilizes thioflavin-stained sections for observation by fluorescent LM, and freeze-dried cryosections for observation by electron and backscattered-electron imaging (SEI, BSI) and quantitative measurement by electron-induced x-ray microanalysis and SIMS.
