Department of Neurology, Boston University School of Medicine, Boston, MA 20008, USA.
J Alzheimers Dis. 2013;33 Suppl 1(0 1):S439-45. doi: 10.3233/JAD-2012-129040.
The study of Alzheimer's disease (AD) in the Framingham Heart Study (FHS), a multi-generational, community-based population study, began nearly four decades ago. In this overview, we highlight findings from seven prior publications that examined lifetime risk estimates for AD, environmental risk factors for AD, circulating and imaging markers of aging-related brain injury, and explorations on the genetics underlying AD. First, we describe estimations of the lifetime risk of AD. These estimates are distinguished from other measures of disease burden and have substantial public health implications. We then describe prospective studies of environmental AD risk factors: one examined the association between plasma levels of omega-3 fatty-acid and risk of incident AD, the other explored the association of diabetes to this risk in subsamples with specific characteristics. With evidence of inflammation as an underlying mechanism, we also describe findings from a study that compared the effects of serum cytokines and spontaneous production of peripheral blood mononuclear cell cytokines on AD risk. Investigating AD related endophenotypes increases sensitivity in identifying risk factors and can be used to explore pathophysiologic pathways between a risk factor and the disease. We describe findings of an association between large volume of white matter hyperintensities and a specific pattern of cognitive deficits in non-demented participants. Finally, we summarize our findings from two genetic studies: The first used genome-wide association (GWA) and family-based association methods to explore the genetic basis of cognitive and structural brain traits. The second is a large meta-analysis GWA study of AD, in which novel loci of AD susceptibility were found. Together, these findings demonstrate the FHS multi-directional efforts in investigating dementia and AD.
弗雷明汉心脏研究（FHS）是一项多世代、以社区为基础的人群研究，对阿尔茨海默病（AD）的研究始于近四十年前。在本篇概述中，我们重点介绍了之前发表的七项研究的结果，这些研究检查了 AD 的终身风险估计、AD 的环境风险因素、与衰老相关的脑损伤的循环和成像标志物，以及 AD 潜在遗传学的探索。首先，我们描述了 AD 终身风险的估计。这些估计与其他疾病负担指标不同，具有重要的公共卫生意义。然后，我们描述了 AD 环境风险因素的前瞻性研究：一项研究检查了ω-3 脂肪酸的血浆水平与 AD 发病风险之间的关联，另一项研究则在具有特定特征的亚组中探索了糖尿病与这种风险的关系。鉴于炎症是一种潜在机制，我们还描述了一项比较血清细胞因子和外周血单个核细胞细胞因子自发产生对 AD 风险影响的研究结果。研究 AD 相关的表型可以提高识别风险因素的敏感性，并可用于探索风险因素与疾病之间的病理生理途径。我们描述了在非痴呆参与者中，大脑白质高信号体积大与特定认知缺陷模式之间存在关联的研究结果。最后，我们总结了两项遗传研究的发现：第一项研究使用全基因组关联（GWA）和基于家族的关联方法探索认知和结构脑特征的遗传基础。第二项是一项关于 AD 的大型 GWA 荟萃分析研究，其中发现了 AD 易感性的新基因座。总之，这些发现展示了 FHS 在研究痴呆和 AD 方面的多方位努力。
