Oral Session

Oral Session 15 一般口演15

O15-1 Conformational conversion of alpha-Synuclein monomer regulates the distinct types of fibril formations シヌクレインモノマーの構造変換が規定するシヌクレイノパチーの多様性について Ikenaka Kensuke（池中建介）¹，Cesar Aguirre²，宗正智²，角田渓太¹，後藤祐児²，望月秀樹¹ ¹University of Osaka,School of Med, Dept. Neurology ²Osaka Univ. Insit. of Protein Research Aggregation of α-synuclein (aSyn) is a pathological hallmark of several neurodegenerative disorders including Parkinson’s disease (PD), Lewy body disease, and Multiple system atrophy (MSA). Although they are caused by accumulation of a same protein, their clinical and pathological features are totally distinct. Recent studies suggest that variations in a structure of aSyn fibril may associated with the variations in disease phenotypes. Presence of two types of fibril created by the different buffers has been reported and those two types of fibril showed the distinct pathologies when they were injected into the mouse brain, showing the clear evidence that different types of fibril lead to distinct pathologies. However, it has not been clearly understood how the specific process of fibril formation determined and how it affects the final types of fibril.In this study, we unexpectedly found that aSyn create different types of fibril even from a same buffer condition. We used a combination of ThT assay, TEM, SEC, AUC and FTIR and have found two classes of WT-αSyn fibrils with distinctive kinetics and morphologies, namely Type A & B. An analysis of the initial steps of the formation of both fibrils showed that in solution there were two molecular populations in equilibrium that lead to distinct species in the nucleation process. Currently, we are investigating how those molecular equilibriums affect the disease type of synucleinopathy such as PD and MSA, as well as the familial parkinson’s disease with aSyn mutations.		O15-2 Serum soluble TREM2 and risk of dementia: the Hisayama Study 老年期の血清TREM2が認知症発症におよぼす影響：久山町研究 Ohara Tomoyuki（小原　知之）^1,2，神庭　重信¹，浅原哲子³，田中　将志³，山陰一³，日下部徹³，井上隆之³，二宮利治² ¹Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University ²Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University ³Department of Endocrinology, Metabolism, and Hypertension Research, Clinical Research Institute, National Hospital Organization Kyoto Medical Center Background: Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) gene is known as a genetic risk factor for Alzheimer’s disease (AD), but no population-based prospective studies assessed the association of serum soluble TREM2 (sTREM2) levels with the incidence of dementia. Objective: To investigate the association between serum sTREM2 and risk of developing dementia and its subtypes in a general elderly population of Japanese. Methods: A total of 1,349 Japanese community-dwelling elderly without dementia, aged 60 years or older, were followed for 10 years (2002-2012). Serum sTREM2 level was quantified by using a RayBio Human TREM-2 ELISA Kit and divided into quartiles. The hazard ratios (HRs) on the risk of dementia was computed using a Cox proportional hazards model. This study was approved by the Kyushu University Institutional Review Board for Clinical Research. Results: During the follow-up, 300 subjects developed all-cause dementia; 193 had AD, and 85 had vascular dementia (VaD). The age- and sex-adjusted incidences of all-cause dementia, AD, and VaD increased significantly with increasing serum sTREM2 levels (all p for trend <0.05). These increasing trends remained unchanged after adjustment for potential confounding factors. Compared with subjects in the first quartile of serum sTREM2 levels, the multivariable-adjusted risks of developing all-cause dementia, AD, and VaD were significantly higher in those in the fourth quartile (HR=2.03, 95% CI=1.39-2.97, P<0.01 for all-cause dementia; HR=1.62, 95% CI=1.02-2.55, P=0.04 for AD; HR=2.85, 95% CI=1.35-6.02, P<0.01 for VaD). Conclusions: Increased serum sTREM2 is a significant risk factor for the development of all-cause dementia, AD, and VaD in the community-dwelling elderly population.

O15-3 Diosgenin-rich yam extract enhances cognitive function: a placebo-controlled, randomized, double-blind, crossover study of healthy adults ジオスゲニン高濃度含有ヤマイモエキスによる健常人の認知機能向上：ランダム化二重盲検プラセボ対照クロスオーバー試験による検討 Tohda Chihiro（東田千尋）¹，楊熙蒙¹，稲田祐奈²，松井三枝² ¹Division of Neuromedical Science, Institute of Natural Medicine, University of Toyama, Toyama, Japan ²Laboratory of Clinical Cognitive Neuroscience, Institute of Liberal Arts and Science, Kanazawa University, Kanazawa, Japan Diosgenin, a yam-derived compound, was found to facilitate the repair of axonal atrophy and synaptic degeneration and improve memory dysfunction in a transgenic mouse model of Alzheimer's disease. It was also found to enhance neuronal excitation and memory function even in normal mice. We hypothesized that diosgenin, either isolated or in an extract, may represent a new category of cognitive enhancers reinforcing morphologically and functionally neuronal networks. This study aimed to investigate the effects of a diosgenin-rich yam extract (DYE) on cognitive enhancement in healthy volunteers. This placebo-controlled, randomized, double-blind, crossover study was conducted with the approval of the Ethics Committee of the University of Toyama. Each subject signed an informed consent form prior to study entry. Twenty eight healthy volunteers were recruited from Toyama Prefecture, and randomly assigned to receive either a yam extract or placebo. Preliminary functional animal experiments indicated that an oil solvent mediated the most efficient distribution of diosgenin into the blood and brain after oral administration, and was a critical factor in the cognitive benefits. Therefore, test samples (placebo and DYE) were prepared with olive oil. The intake period was 12 weeks, and a 6-week washout period separated the two crossover intake periods. The Japanese version of RBANS test was used for neurocognitive assessment, and adverse effects were monitored through blood testing. DYE consumption for 12 weeks yielded significant increases in total RBANS score. Among the 12 individual standard cognitive subtests, DYE use significantly improved semantic fluency. No adverse effects were detected. The DYE treatment appeared to safely enhance cognitive function in healthy adults.