APPLICATION OF PIXE IN MEDICAL STUDY: ENVIRONMENTAL MINERALS AND NEURODEGENERATIVE DISORDERS

Comparative study on amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PDC) in the Kii Peninsula of Japan and Guam was conducted to evaluate the participatory role of environmental minerals in the pathogenesis of the above neurodegenerative diseases, using particle-induced x-ray emission (PIXE) spectrometry and morphometric-statistical analysis. A significantly high content of Al in the hippocampus and spinal cord of Kii and Guamanian ALS/PD cases was found with a positive correlation for Fe and Cu , and a negative correlation for Zn . The numbers of hippocampal neurons in Guamanian PDC, Alzheimer's disease, and Parkinson's disease were significantly decreased with a high Al content. Al content significantly and positively correlated with the number of Alzheimer's neurofibrillary tangles (NFTs) in the hippocampus of ALS cases and controls in both foci, especially in Guamanian cases. The slope of best linear regression of Guamanian cases was markedly steeper than that of Japanese cases ( p < 0.001). Morin staining for Al showed green fluorescence on the nucleolus, cytoplasm, and NFT in the hippocampus of Kii ALS cases. These findings suggest that Guamanian and Kii people have a predisposition to develop ALS/PDC precipitated by their geological/geochemical environmental status, i.e., a prolonged low intake of Ca and Mg together with excess exposure to Al and other environmental minerals.

ENVIRONMENTAL MINERALS IN KII AMYOTROPHIC LATERAL SCLEROSIS IN JAPAN: A PIXE ANALYSIS FEATURING ALUMINUM

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.

Abstracts of Papers Presented at the 30th Annual Meeting of the Canadian Association of Neuropathologists

H. ITO, A. HIRANO and S.-H. YEN (Bronx, U.S.A.)The parkinsonism-dementia complex (PDC) on Guam is characterized histopathologically by neuronal loss in widespread areas and by the presence of numerous Alzheimer’s neurofibrillary tangles in certain neuron groups. It has been reported that in Guamanian PDC patients there is virtually no plaque formation. Prior to 1965, the existence of argentophilic plaques has been investigated in only a few Guamanian cases. However, from more recent studies, there is evidence on plaque formation in a relatively high proportion of Guamanian patients. To determine whether this change is due to differences in the detection techniques, we have re-evaluated with an immunoperoxidase method the archival material used in earlier studies.