Abstract

To evaluate a participatory role of environmental minerals in the pathogenesis of amyotrophic lateral sclerosis (ALS) in the Kii Peninsula of Japan, one of the three high-incidence foci, elemental and neuropathological investigations of lumbar spinal cord and hippocampal tissues were conducted, using particle-induced x-ray emission (PIXE) spectrometry and histomorphometric analysis. The PIXE analysis revealed extremely high contents of Al in both tissues of Kii ALS cases as compared with sporadic ALS and control cases. Morphometric analysis in the hippocampus showed abundant Alzheimer’s neurofibrillary tangles (NFTs) in the Kii ALS cases as compared with the other cases. Al content significantly correlated with the density of NFTs in all ALS cases ( r =0.765, p < 0.0001). Interestingly, both Al content and density of NFTs in the hippocampus of all ALS cases significantly and negatively correlated with Ca and Mg contents in the birthplace area’s rivers. The extremely low Ca and Mg content in the focus rivers was confirmed along with the high ratio of Al 2 O 3/ CaO in the soil. Thus, Kii ALS patients may reflect the geochemical environment of their birthplace, i.e., long term Ca and Mg deficiencies and excess Al accumulation along with widespread NFT formation in the brain.

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