重磅:华人科学家发现阿尔茨海默病的源头或可追溯到出生前

2017-02-18 周伦 奇点

近期,来自加拿大不列颠哥伦比亚大学(University of British Columbia)的宋伟宏教授团队和重庆医科大学附属儿童医院的李廷玉教授团队,在阿尔茨海默病开始的时间这个问题上,有了最新的惊人发现:如果胎儿或新生儿没有获得足够的维生素A,导致阿尔茨海默病的生物化学反应可能在婴儿还在子宫内或刚出生后就开始了。他们的这一重要研究成果刊登在神经学领域的著名期刊《Acta Neuropat



一直以来,很多人都将阿尔茨海默病叫做老年痴呆,一是因为阿尔茨海默病患者以65岁以上的老年人为主,二是因为阿尔茨海默病在老年痴呆中占的比例相当大。所以很多时候,老年痴呆俨然已经成了阿尔茨海默病的代名词。

然而,关于阿尔茨海默病开始的时间,学界却一直莫衷一是。有研究表明,导致阿尔茨海默病的β淀粉样蛋白在症状出现之前的30年左右(1),就已经开始形成并富集了。这样算来,大部分患者大脑开始产生β淀粉样蛋白的时间大概在35岁左右。

近期,来自加拿大不列颠哥伦比亚大学(University of British Columbia)的宋伟宏教授团队和重庆医科大学附属儿童医院的李廷玉教授团队,在阿尔茨海默病开始的时间这个问题上,有了最新的惊人发现:如果胎儿或新生儿没有获得足够的维生素A,导致阿尔茨海默病的生物化学反应可能在婴儿还在子宫内或刚出生后就开始了。他们的这一重要研究成果刊登在神经学领域的著名期刊《Acta Neuropathologica》上(2)。

重庆医科大学附属儿童医院的李廷玉教授重庆医科大学附属儿童医院的李廷玉教授

毕业于重庆医科大学的宋伟宏教授,现任加拿大阿尔茨海默病首席研究员,他在阿尔茨海默病和唐氏综合症的发病机制和药物开发及治疗领域建树颇丰,2012年他入选加拿大健康科学院院士。李廷玉教授是我国儿童营养和生长发育领域的专家,曾任重庆医科大学附属儿童医院院长。

实际上,维生素A在人体的生长发育中起到了非常关键的作用,参与到视觉和免疫系统的形成,红细胞的生成,骨骼的生长等多个重要环节。此次,宋教授和李教授学科优势互补,一举破解维生素A与阿尔茨海默病之间的关系,且看他们是如何研究的。

他们在研究一开始,对重庆市650名老人的认知状况做了调查,他们发现在维生素A轻度或重度缺乏老年人群体中,有75%的人存在认知障碍的症状,而在维生素A摄入正常的老年人群体中,只有47%的人受到认知障碍的困扰。虽然之前有研究表明,维生素A缺乏与阿尔茨海默病有关,但是如此显着的差异,还是让研究团队吃惊不小。

于是他们决定做一点事情。虽然维生素A缺乏与阿尔茨海默病存在相关性并不新鲜,但是学界一直不清楚维生素A缺乏是如何引起阿尔茨海默病的。这个问题显然吸引了以探究发病机制为专长的宋伟宏教授的兴趣。

于是他们从强生实验室(Jackson Laboratory)购买了携带导致阿尔茨海默病基因的模式小鼠。由于轻度或者边缘性的维生素A缺乏(Marginal vitamin A deficiency ,MVAD)在当前的社会条件下更流行,因此他们打算研究边缘性的维生素A缺乏对阿尔茨海默病病程的影响。

通过给这些小鼠喂食维生素A含量不同的食物,他们发现模式小鼠无论在出生前,还是出生后经历边缘性的维生素A缺乏,大脑都会出现因β淀粉样蛋白富集形成的斑块。而且出生前即遭遇边缘性的维生素A缺乏的模式小鼠,由于在胚胎发育期间β淀粉样蛋白斑块就损坏了附近的神经元,导致小鼠学习和认知缺陷更严重。

对于那些在子宫内就遭遇维生素A缺乏的小鼠而言,当它们出生一段时间之后,给它们食用维生素A正常的食物,它们的各项表现也比出生后才遭遇维生素A缺乏的小鼠差。这意味着仅仅喂食这些小鼠维生素A正常的食物,不足以让小鼠恢复学习和记忆能力。

那这些小鼠的认知能力还有的救吗?于是他们又搞了一套维生素A缺乏治疗方案。他们最终发现,如果让在子宫内遭遇维生素A缺乏的小鼠出生后及时补充维生素A,还是可以挽回部分损伤。而且,治疗的越早越好。

据研究论文介绍,这是研究人员第一次发现边缘性的维生素A会导致β淀粉样蛋白积累,最终损害认知能力的证据。

尽管维生素A没有引起太多人的注意,但是这并不代表这个问题不严重。据世界卫生组织统计,全世界估计有2亿儿童和2000万孕妇存在不同程度的维生素A缺乏症。

随着社会的不断进步,人们生活水平的不断提高,现在严重缺乏维生素A的群体在逐渐减小,而边缘性的维生素A缺乏却越来越普遍。主要原因之一便是,MVAD的临床表现不是那么明显,很容易被忽视。

但是学界和医疗界从来都没有忽略这个问题。宋教授和李教授团队的研究,再次强调了维生素A缺乏的严重性。饱受阿尔茨海默病折磨的人类,必定会重视维生素A缺乏的问题。

另外,也有很多科学家在想办法解决这个问题。例如前几年饱受争议的「黄金大米」就是科学家提出的一个解决办法。

当然,面对这个问题,我们也不必恐慌,一味的盲目补充维生素A。我们应该在医生的指导下,合理的补充维生素A。另外,维生素A的代谢相关基因也比较清楚了,合理的基因检测,也有助于我们了解自己维生素的代谢情况。毕竟过量的维生素A也是有毒的。

原始出处
(1)Masters, C. L., et al. (2015). Alzheimer’s disease. Nature Reviews Disease Primers: 15056.
(2)Zeng, J., et al. (2017). Marginal vitamin A deficiency facilitates Alzheimer’s pathogenesis. Acta Neuropathologica: 1-16.
(3)Sommer A, West KP (1996). Vitamin A deficiency: health, survival and vision. Oxford University Press, Oxford

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    2017-02-20 xxxx1054
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