A condition of unbalanced minerals was found in soil and drinking water from three amyotrophic lateral sclerosis (ALS) foci on Guam, in the Kii Peninsula and in West New Guinea with a low concentration of calcium and magnesium coupled with a high concentration of aluminum and manganese. The current epidemiological studies in the Western Pacific including the Kii Peninsula of Japan, have suggested that environmental factors contribute to the pathogenetic process of ALS and parkinsonism-dementia (PD). Six Kii cases with ALS showed higher Ca and lower Mg contents in the central nervous system (CNS) tissues than those of neurologically normal controls. We subsequently designed an animal study to experimentally ascertain the mineral or metal deposition in CNS tissues under various dietary regimens using rats. The experimental results suggest that unbalanced minerals and/or metals lead to the accumulation not only of Ca, but also Mn, and Al, and diminution of Mg and Zn in CNS tissues of rats and humans on these dietary regimens, with implication for long-term neuronal degeneration and accumulating CNS deficit.