The role of aluminum in the etiology of Alzheimer's disease remains controversial because of the contradictory results reported by the many laboratories in the field. Many of the laboratories relied on fixatives and stains 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 has been developed that permits the unambiguous identification of plaques and NFTs in unfixed, unstained sections, that does not alter the elemental distributions, and that provides detectability and rapid imaging of the aluminum distribution at concentrations in the ppm range. This methodology uses thioflavin-stained sections for observation by fluorescent LM, and freeze-dried cryosections for observation by backscattered-electron imaging (BSI) and for quantitative measurement by electron-induced X-ray micro-analysis and SIMS. No aluminum above the normal background concen-tration has been observed in tangled neurons in sections prepared by this method. However, a marked increase in sulphur relative to phosphorus has been observed in NFTs, and of Fe in plaques.
