Omega-3, isoflavones & amyloid deposition in cognitively normal elderly Japanese

 描述（由申请人提供）：神经影像学的最新进展使得使用匹兹堡化合物B（PiB）评价脑中淀粉样蛋白沉积成为可能。淀粉样蛋白沉积是阿尔茨海默病（AD）的独立危险因素。大多数80-89岁的认知正常（NC）的老年人有淀粉样蛋白沉积。没有研究发现老年NC患者中淀粉样蛋白沉积的患病率较低。找到这样的人群是确定AD风险因素的第一步。日本人的寿命最长;虽然他们的载脂蛋白E4（AD的主要遗传风险因素）的患病率与美国相似，但日本人的饮食却有相当大的不同，其特点是在过去50年中海洋omega-3脂肪酸（omega-3 FAs）和大豆异黄酮（ISF）的饮食摄入量明显较高（两者都比美国高10倍以上）。许多观察性研究报告称，omega-3脂肪酸的饮食摄入量与痴呆和AD的发病率呈负相关。日本最近的一项研究报告说，大豆的高饮食摄入量是ISF的来源，与痴呆症和AD的发病率呈负相关。来自少数老年NC志愿者的证据表明，日本人淀粉样蛋白沉积的患病率非常低。我们假设：1）80- 89岁的日本老年NC患者大脑中淀粉样蛋白沉积的患病率显著低于美国患者; 2）在80-89岁的日本老年NC患者中，中年血清中每种omega-3 FA和ISF水平与晚年淀粉样蛋白沉积显著负相关。为了检验我们的假设，我们将招募200名年龄在80-89岁的日本男性和女性（各100名），从日本的Suita研究中随机选择NC：1994年基线年龄在30-79岁的6，406名受试者的基于人群的前瞻性队列研究。我们将检查这200名受试者的PiB标准化到美国研究。我们还将使用储存的血清样本来检查中年时omega-3脂肪酸和ISF水平与老年淀粉样蛋白沉积的关系。大脑中淀粉样蛋白沉积的低患病率和ω-3脂肪酸和/或ISF与淀粉样蛋白沉积的显著负相关性的发现将对AD病因学的研究和潜在的预防产生重大影响。

 DESCRIPTION (provided by applicant): Recent progress in neuroimaging has made it possible to evaluate amyloid deposition in the brain with Pittsburgh compound B (PiB). Amyloid deposition is an independent risk factor for Alzheimer's disease (AD). The majority of elderly aged 80-89 with normal cognition (NC) have amyloid deposition. No studies have found a population where prevalence of amyloid deposition is low among elderly with NC. Finding such a population is a first step to identifying risk factors for AD. Japanese have the greatest longevity; while their prevalence of apolipoprotein E4, the major genetic risk factor for AD, is similar to the US, Japanese have a considerably different diet characterized by markedly high dietary intake of marine omega-3 fatty acids (omega-3 FAs) and soy isoflavones (ISF) (both are >10x higher than in the US) for the past 50 years. Many observational studies reported that dietary intake of omega-3 FAs is inversely associated with incident dementia and AD. A recent study in Japan reported that high dietary intake of soy, which is the source of ISF, is inversely associated with incident dementia and AD. Suggested evidence from a small number of elderly volunteers with NC shows that Japanese have very low prevalence of amyloid deposition. We hypothesize that 1) Japanese elderly aged 80- 89 with NC have significantly lower prevalence of amyloid deposition in the brain than in the US and 2) in Japanese elderly aged 80-89 with NC, midlife serum levels of each of omega-3 FAs and ISF have significant inverse associations with late-life amyloid deposition. To test our hypotheses, we will enroll 200 Japanese men and women (100 each) aged 80-89 with NC randomly selected from the Suita Study in Japan: a population- based prospective cohort study of 6,406 subjects aged 30-79 at baseline in 1994. We will examine these 200 subjects for PiB standardized to US studies. We will also examine the association of midlife levels of each of omega-3 FAs and ISF with late-life amyloid deposition using stored serum samples. The findings of low prevalence of amyloid deposition in the brain and significant inverse associations of omega-3 FAs and/or ISF with amyloid deposition will have major impact on research into the etiology and potentially the prevention of AD.