Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer's disease: A laser microprobe (LAMMA) study

Authors

  • Paul F. Good BS,

    1. Department of Pathology (Neuropathology Division), Mount Sinai School of Medicine, New York, NY
    2. Arthur M. Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, NY
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  • Dr Daniel P. Perl MD,

    Corresponding author
    1. Department of Pathology (Neuropathology Division), Mount Sinai School of Medicine, New York, NY
    2. Arthur M. Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, NY
    3. Department of Psychiatry, Mount Sinai School of Medicine, New York, NY
    • Neuropathology Division, Box 1134, Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029
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  • Linda M. Bierer MD,

    1. Department of Psychiatry, Mount Sinai School of Medicine, New York, NY
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  • James Schmeidler PhD

    1. Department of Psychiatry, Mount Sinai School of Medicine, New York, NY
    2. Department of Biomathematical Sciences, Mount Sinai School of Medicine, New York, NY
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Abstract

We report the results of an examination of the elemental content of neurofibrillary tangle–bearing and neurofibrillary tangle–free neurons identified within the hippocampus of 10 subjects with Alzheimer's disease and 4 neuropathologically intact age-matched control subjects. The study employed laser microprobe mass analysis (LAMMA), a technique that provides extremely sensitive multielement detection in plastic-embedded, semithin-sectioned tissues. Evidence for the selective accumulation of aluminum within the neurofibrillary tangle–bearing neurons was obtained in all 10 subjects with Alzheimer's disease. The site of aluminum deposition within these cells was the neurofibrillary tangle itself, and not the “nuclear region”, as we previously reported. Iron accumulation was also detected within neurofibrillary tangles. Evaluation for the accumulation of other elements within the tangle-bearing neurons failed to reveal any other metallic element as being consistently present. In addition, probe sites directed to neurons identified in snapfrozen cryostat sections from 2 subjects with Alzheimer's disease revealed similar spectra with prominent aluminum-related peaks, confirming that our findings are not related to exogenous contamination through fixation, embedding, or other procedures prior to analysis. This study further confirms the association of aluminum and neurofibrillary tangle formation in Alzheimer's disease.

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