Intraneuronal Aluminum Accumulation in Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia of Guam

Abstract

Scanning electron microscopy with energy-dispersive x-ray spectrometry was used to analyze the elemental content of neurofibrillary tangle (NFT)-bearing and NFT-free neurons within the Sommer's sector (H1 region) of the hippocampus in Guamanian Chamorros with amyotrophic lateral sclerosis and parkinsonism-dementia and in neurologically normal controls. Preliminary data indicate prominent accumulation of aluminum within the nuclear region and perikaryal cytoplasm of NFT-bearing hippocampal neurons, regardless of the underlying neurological diagnosis. These findings further extend the association between intraneuronal aluminum and NFT formation and support the hypothesis that environmental factors are related to the neurodegenerative changes seen in the Chamorro population.

Aluminum Enhances Iron Uptake and Expression of Neurofibrillary Tangle Protein in Neuroblastoma Cells

“…NFT-bearing neurons are also found after the injection of A1 salts into the brains of experimental animals (Troncoso et al, 1986;Kowall et al, 1989). NFTs are also found in patients with AD, dialysis patients with Alinduced DD (Brun and Dictor, 1981;Scholtz et al, 1987;Candy et al, 1992), and patients with parkinsonism dementidamyotropic lateral sclerosis of Guam (Per1 et al, 1982;Garmto et al, 1986), which is associated with increased brain A1 concentration. However, the location of NFT-bearing neurons in brain of these diverse Alassociated disorders differs.…”

Neurotoxicology of the Brain Barrier System: New Implications

“…Exposure to aluminum in laboratory animals results in the development of neurofibrillary tangles and degeneration of cerebral neurons. Although part of this effect represents direct toxicity of aluminum on neuronal pathways, aluminum ions also possess a high affinity for cerebral endothelia (10). Following exposure, aluminum-facilitated passage of endogenous, behaviorally active peptides across the BBB was noted (11).…”

The promotion of iron-induced generation of reactive oxygen species in nerve tissue by aluminum

“…Lipid peroxidation rates are also elevated in autopsy samples of Alzheimer cortex (Subbarao et al, 1990), and there is other evidence of an association between this disease and oxidative stress (Pappola et al, 1992). Excess levels of iron together with aluminum have also been found in the substantia nigra of Parkinsonian patients (Hirsch et al, 1991), and aluminum accumulates within neurons in amyotrophic lateral sclerosis-Parkinsonian dementia of Guam (Perl et al, 1982).…”