| Laser microprobe mass spectrometry (LMMS) has been used to determine aluminum (Al), calcium (Ca) and iron (Fe) content at the cellular level in the hippocampus of Alzheimer's disease (AD), dialysis dementia (DD) and control subjects. Additionally, human hippocampal cell cultures which were subjected to acute Al exposure have been analyzed. Quantitation of the LMMS tissue analysis data was achieved through comparison to working calibration curves prepared for each element utilizing cis dicyclohexano - 18 - crown - 6 ether coordination complexes. The major goals of this work were: (1) Statistical comparison of elemental levels in degenerating neurons (NFT-bearing) as compared to non-degenerating neurons (NFT-free) from within the same subject and the comparison of both types of AD neurons to normal neurons from neurological controls. (2) Statistical comparison of DD values to control and AD values. (3) Analysis of hippocampal cell cultures to determine if acute Al exposure alone is enough to induce cellular uptake. (4) Quantitation of LMMS data for the elements of interest.; Statistical comparison of the various cellular components indicated no significant (p {dollar}<{dollar} 0.05) AD/control differences existed for Al. However Al was significantly elevated in DD cytoplasm compared to NFT-bearing, NFT-free and control cytoplasm. Fe was found to be significantly (p {dollar}<{dollar} 0.05) elevated in DD cytoplasm, nuclei and neuropil as compared to AD and control levels. Fe was marginally (p {dollar}<{dollar} 0.10) increased in AD neuropil compared to control. Ca indicated no consistent imbalances. Statistical analysis of the cell culture data indicated Al exposure alone was not enough to induce excess cellular uptake. Calculation of correlation coefficients between cytoplasm and nucleus levels indicated positive correlations for Al and Fe for AD, DD and control subjects.; Use of cis dicyclohexano - 18 - crown 6 ether coordination complexes dissolved in tissue embedding medium as standards allowed the preparation of calibration curves with correlation coefficients of 0.98 or greater.; Comparison of the AD/control findings with previous literature reports along with a discussion of the effectiveness of coordination complexes in the quantitation of LMMS tissue analysis data will be presented, as will a discussion of the possible importance of these elemental imbalances in the etiology and pathogenesis of AD. |
