An investigation of the role of brain amyloid in cognition, brain atrophy and Alzheimer s disease in Down s syndrome

脑淀粉样蛋白在唐氏综合症认知、脑萎缩和阿尔茨海默病中作用的研究

• 批准号: G1002252/1
• 负责人: Anthony Holland
• 金额: $ 128.72万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1002252%2F1
• 关键词: investigation; role; brain; amyloid; cognition

In the UK there are about 60,000 people with Down s syndrome (DS). Like the general population, people with DS are living longer. As a group they have the highest age-related risk for developing dementia due to Alzheimer?s disease (AD) at a relatively young age - 50% of people with DS develop AD by the age of 59 years (compared to less than 1% of the general population). This places a great burden on individuals, families and society.We do not know what causes AD but there is evidence that an excess deposition of a protein called beta-amyloid in the brain is a culprit early in the disease process resulting in a cascade of effects on the brain and in brain-cell death (observed in AD) and dementia. People with DS produce beta-amyloid in excess as they are born with an extra copy of the gene coding for the precursor of beta-amyloid. Post-mortem studies of brain tissue from people with DS have revealed that beta-amyloid is widely present at a very young age and is found in all who are in their forties or older. A recently developed method for detecting beta-amyloid deposition using PET (positron emission tomography) brain scanning technology together with a beta-amyloid tracer (Pittsburgh Compound-B) can safely and reliably measure the amount and distribution of beta-amyloid in the brain during life. Studies have been done in AD affecting the general population but none in people with DS.We have completed a pilot study using this technique and found that it was acceptable to people with DS, and it can detect beta-amyloid in their brains. We are now proposing a clinical study with 60 participants using this technique to help us answer questions about the effect that excess beta-amyloid has on the brain and on mental (or cognitive) functioning (e.g. memory), and the risk of dementia. Together with the use of specific cognitive assessments, we will scan people with DS once at the start and again after two years. We will investigate the relationship between cerebral amyloid deposition, brain atrophy and cognitive decline and dementia. New potentially preventative treatments are being developed for AD that target amyloid turnover in the brain. This study will inform such developments and people with DS may be the first to benefit if they are safe and effective. Observations in people with DS may also inform treatments of AD in the general population.

在英国，大约有60,000人患有唐氏综合症（DS）。与普通人群一样，DS患者的寿命更长。作为一个群体，他们有最高的年龄相关的风险发展痴呆症由于阿尔茨海默病？DS疾病（AD）在相对年轻的年龄- 50%的DS患者在59岁时发展为AD（相比之下，一般人群的不到1%）。这给个人、家庭和社会带来了巨大的负担。我们不知道是什么导致了AD，但有证据表明，大脑中一种称为β-淀粉样蛋白的蛋白质的过量沉积是疾病过程早期的罪魁祸首，导致对大脑的级联效应，并导致脑细胞死亡（在AD中观察到）和痴呆症。患有DS的人产生过量的β-淀粉样蛋白，因为他们天生就有一个额外的β-淀粉样蛋白前体基因编码拷贝。对DS患者脑组织的尸检研究表明，β-淀粉样蛋白在非常年轻的时候就广泛存在，并且在所有40多岁或更老的人中都有发现。最近开发的一种使用PET（正电子发射断层扫描）脑扫描技术和β-淀粉样蛋白示踪剂（匹兹堡化合物-B）检测β-淀粉样蛋白沉积的方法可以安全可靠地测量生命期间大脑中β-淀粉样蛋白的数量和分布。已经对影响普通人群的AD进行了研究，但没有对DS患者进行研究。我们已经完成了一项使用该技术的试点研究，发现DS患者可以接受该技术，并且可以检测他们大脑中的β淀粉样蛋白。我们现在提出了一项临床研究，有60名参与者使用这种技术来帮助我们回答有关过量β-淀粉样蛋白对大脑和精神（或认知）功能（例如记忆）的影响以及痴呆症风险的问题。结合特定的认知评估，我们将在开始时对DS患者进行一次扫描，两年后再进行一次扫描。我们将探讨脑淀粉样蛋白沉积、脑萎缩和认知能力下降与痴呆之间的关系。正在开发针对AD的新的潜在预防性治疗方法，其目标是大脑中的淀粉样蛋白周转。这项研究将告知这些发展，如果他们是安全和有效的，DS患者可能是第一个受益者。DS患者的观察结果也可能为一般人群中AD的治疗提供信息。