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

在英国大约有6万人患有唐氏综合症（DS）。和一般人一样，退行性痴呆患者寿命更长。作为一个群体，他们患老年痴呆症的年龄相关风险最高？老年痴呆症（AD）在相对年轻的时候发病——50%的退行性椎体滑移患者在59岁时患上AD（相比之下，一般人群中这一比例不到1%）。这给个人、家庭和社会带来了巨大的负担。我们不知道阿尔茨海默病的病因，但有证据表明，在疾病早期，一种叫做β -淀粉样蛋白的蛋白质的过量沉积是罪魁祸首，它会对大脑产生一连串的影响，导致脑细胞死亡（在阿尔茨海默病中观察到）和痴呆。患有DS的人会产生过多的β -淀粉样蛋白，因为他们天生就有一个额外的β -淀粉样蛋白前体编码基因拷贝。对退行性痴呆患者脑组织的尸检研究表明，-淀粉样蛋白广泛存在于非常年轻的年龄，并且在所有40多岁或以上的人身上都有发现。最近开发的一种检测β -淀粉样蛋白沉积的方法，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）可以安全可靠地测量一生中大脑中β -淀粉样蛋白的数量和分布。人们已经对阿尔茨海默病对普通人群的影响进行了研究，但没有对退行性椎体滑移患者进行过研究。我们已经用这项技术完成了一项初步研究，发现它对退行性痴呆患者是可以接受的，它可以检测他们大脑中的-淀粉样蛋白。我们现在提议对60名参与者进行一项临床研究，利用这项技术来帮助我们回答有关过量的β -淀粉样蛋白对大脑和精神（或认知）功能（如记忆）的影响以及痴呆症风险的问题。在使用特定的认知评估的同时，我们将在一开始对患有退行性痴呆的人进行一次扫描，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、认知能力下降和痴呆之间的关系。针对阿尔茨海默病的新的潜在预防性治疗方法正在开发，其目标是大脑中的淀粉样蛋白转换。这项研究将为这些发展提供信息，如果退行性椎体滑移症患者安全有效，他们可能是第一个受益的人。对退行性椎体滑移患者的观察也可以为一般人群的AD治疗提供信息。

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.