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60,000名患有唐氏综合症(DS)的人。与普通人群一样，患有DS的人寿命更长。作为一个群体，他们在相对较年轻的年龄就有最高的年龄相关风险患上阿尔茨海默病-S病(AD)--50%的DS患者在59岁时患上AD(相比之下，总人口的这一比例不到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，大脑中一种名为β-淀粉样蛋白的蛋白质过度沉积是疾病过程早期的罪魁祸首，导致对大脑的一系列影响，并导致脑细胞死亡(在阿尔茨海默病中观察到)和痴呆症。患有DS的人会产生过量的β-淀粉样蛋白，因为他们天生就有一个额外的编码β-淀粉样蛋白前体的基因副本。对DS患者脑组织的尸检研究表明，β-淀粉样蛋白在很小的年龄就广泛存在，并在40多岁或更年长的人中发现。最近开发的一种使用正电子发射断层扫描(PET)脑扫描技术结合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过程中β-淀粉样蛋白在大脑中的数量和分布。已经在AD中进行了影响普通人群的研究，但还没有在DS患者中进行研究。我们已经完成了一项使用这项技术的试点研究，发现DS患者可以接受它，并且它可以检测到他们大脑中的β-淀粉样蛋白。我们现在正在提议一项有60名参与者参与的临床研究，使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(例如记忆)的影响以及痴呆症风险的问题。结合使用特定的认知评估，我们将在开始时扫描一次DS患者，并在两年后再次扫描。我们将研究大脑淀粉样蛋白沉积、脑萎缩与认知功能减退和痴呆的关系。针对阿尔茨海默病的新的潜在预防性治疗方法正在开发中，其目标是大脑中的淀粉样蛋白转化。这项研究将为这些进展提供信息，如果DS患者安全有效，他们可能是第一个受益的人。对DS患者的观察也可能为普通人群中AD的治疗提供参考。

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.