Understanding mechanisms and seeking novel biomarkers in Alzheimer's disease

在过去一年的报告期内，我们发表了与FTO基因常见变异相关的肥胖遗传风险与几种中间表型之间的关系，如冲动、饮食模式和衰老期间的大脑功能。如果我们要开发针对肥胖等与生活方式相关的风险因素的行为干预措施，了解肥胖背后的遗传风险的多效性效应至关重要。 我们研究了中年肥胖与阿尔茨海默病发病年龄的关系及其与AD病理的关系。 在我们的生物标志物研究中，我们报道了阿尔茨海默病(AD)患者血浆中三种磷脂酰胆碱分子的缺失。我们随后扩展了这些发现，以测试它们与非痴呆老年人认知功能下降轨迹的相关性。多平台代谢组学方法结合质谱学和核磁共振已被应用于发现阿尔茨海默病患者的脑脊液黄褐斑生物标志物。

Over the reporting period for the last year, we have published on the relationships between genetic risk for obesity associated with a common variant in the FTO gene and several intermediate phenotypes such as impulsivity, dietary patterns and brain function during aging. Understanding the pleiotropic effects of genetic risk underlying obesity is critical if we are to develop behavioral interventions targeting life-style related risk factors such as obesity. We have examined the relationships between midlife obesity and the age-at-onset of AD as well as its relationship with AD pathology. In our biomarker studies, we have reported on the depeletion of three phosphatidylcholine molecules in the plasma of patients with Alzheimer's disease (AD). We have subsequently extended these findings to test their association with trajectories of cognitive decline in non-demented older individuals. A multi-platform metabolomics approach using mass spectrometry and nuclear magnetic resonance has been applied to discover cerebrospinal fulid biomarkers in AD.