京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第21826号 / 農博第2339号 / 新制||農||1067(附属図書館) / 学位論文||H31||N5198(農学部図書室) / 京都大学大学院農学研究科地域環境科学専攻 / (主査)准教授 髙橋 知之, 教授 北山 兼弘, 准教授 刑部 正博 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

Alzheimer’s disease accounts for up to 80% of the cases of dementia making it the most common type of dementia. As of 2015, 46.8 million people are suffering from Alzheimer’s disease worldwide with an alarming rate of increase in the onset of the disease. Despite the ongoing research, the true cause of Alzheimer’s disease remains unknown. Aluminum is one of the major environmental toxins linked to the etiology of Alzheimer’s disease. A pilot clinical study for non-invasive measurement of bone aluminum was performed at the in vivo neutron activation analysis facility at McMaster University including 15 Alzheimer’s and 15 control subjects. A significant difference in bone aluminum, relative to calcium, was found between the two groups. Multiple methods of analysis were investigated to determine the method with the lowest minimum detection limit. The method of in vivo neutron activation analysis allows for the simultaneous activation of multiple elements. As such, it was possible to measure the magnesium levels, which has been shown to be involved in Alzheimer’s disease, in the study subjects. The results of bone measurements did not show a significant association between bone magnesium levels and Alzheimer’s disease. Moreover, the short-term kinetic behaviours of sodium and chlorine, both essential for the human body, were studied. The outcome of this study revealed an increase in the biological half-lives of sodium and chlorine with age and a higher variability in Alzheimer’s patients compared to control subjects. Finally, bone samples from parenteral nutrition patients were analyzed to determine their aluminum content for comparison and benchmarking purposes. The present results suggest a possible association between bone aluminum and the presence of Alzheimer’s disease. No such association was found for magnesium or the biological half-lives of sodium and chlorine. The technique of in vivo neutron activation analysis was shown to be a promising tool for measuring bone aluminum and magnesium; however, a better detection limit is required to strengthen the current results. / Dissertation / Doctor of Philosophy (PhD) / Alzheimer’s disease is the most common form of dementia. The cause of Alzheimer’s disease is unknown, but both genetic and environmental factors are known to be involved. Different elements have been studied for their possible role in this disease. Aluminum and to a lesser extent magnesium have been linked to the etiology of Alzheimer’s disease. The current thesis presents the results of a clinical study that utilizes the method of in vivo neutron activation analysis to measure aluminum and magnesium in the hand bone of Alzheimer’s disease and control subjects. In vivo neutron activation analysis is a non-invasive method that uses neutrons to activate elements in the human body and measures the radiation emitted. Different methods of analyzing the resulting data were investigated to find the most suitable analysis approach. The biological half-lives of sodium and chlorine were also measured to investigate their short-term kinetic behaviour and pattern with age.

In this thesis the enriched stable isotope marking technique was examined to determine its validity and effectiveness in marking of Lake Sturgeon fin rays. The enriched stable isotope marking technique uses stable isotopes of elements that replace calcium in boney tissue, which are fixed in nature, however in laboratory settings can be easily manipulated. Manipulated ratios of naturally occurring isotopes can be determined from a small sample of the fin ray, thus allowing for the discrimination of fish stocks. Further, the thesis examined the underlying assumptions for strontium and barium into the Lake Sturgeon. For the marking technique to work, strontium and barium must be taken up from the environment and accumulated long-term in boney tissue. Net flux and tissue retention of strontium is reported and the research has demonstrated that enriched stable isotopes can be successfully used to mark the fin ray of Lake Sturgeon for long-term stock discrimination. / October 2015