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

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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.