New £2.5 million consortium to investigate link between Alzheimer’s disease and Down’s syndrome

The London Down Syndrome Consortium - LonDownS - will bring together researchers from across the capital's universities and from disciplines that include adult and child psychiatry, cognitive neuroscience, genetics, and stem cell research. This five-year study, which is due to begin at the start of December, is being funded by a £2.5 million Strategic Award from the Wellcome Trust.

Adults with Down's syndrome are at greater risk of developing Alzheimer's disease than the general population and onset tends to occur at an earlier age. One reason for this is believed to be the fact that one of the key genes implicated in Alzheimer's - the amyloid beta (A4) precursor protein, or APP, gene - is found on chromosome 21; people with Down's syndrome carry three copies of this chromosome.

Alzheimer's disease involves the build-up of amyloid beta 'plaques' in the brain, potentially leading to a gradual loss of brain function, confusion and the complete loss of short-term and long-term memory. However, a significant proportion of people who develop Alzheimer's disease will show no symptoms, even though autopsies reveal they have the build-up of plaques characteristic of the disease.

LonDownS is being led by Dr André Strydom, an adult clinical psychiatrist at UCL (University College London). Together with his collaborators, he will be working with three cohorts of people with Down's syndrome: infants, young adults, and adults aged 45 and above.

"There are some unusual characteristics of Alzheimer's, such as the link with Down's syndrome and the fact that some cases are asymptomatic, that may in fact provide a key to understanding the disease," says Dr Strydom. "Our Consortium will use a variety of disciplines to help us investigate the link between Down's syndrome and Alzheimer's disease.

"We hope the insights this provides will help us diagnose the disease sooner and design novel treatments to benefit people with Down's syndrome, as well as those with Alzheimer's disease."

Participants from the cohorts will be asked for DNA samples, which will be used to identify the genes involved in cognitive function and ageing in Down's syndrome, and to identify which genes increase the risk of developing Alzheimer's disease and which offer protection. This work will be led by Professor John Hardy, also from UCL.

Professor Dean Nizetic from Queen Mary, University of London, will use this knowledge to develop stem cells with characteristics of Down's syndrome. Stem cells are the body's master cells, which can develop into specialised cells; they can be used to identify mutations in genes that affect the cells' behaviour in culture.

The researchers will study the function of analogous genes in mice, developed by Professor Elizabeth Fisher from UCL and Dr Victor Tybulewicz from the Medical Research Council's National Institute for Medical Research, to model Down's syndrome. These mice carry an almost complete extra copy of human chromosome 21.

Professor Annette Karmiloff-Smith at Birkbeck's Centre for Brain and Cognitive Development, University of London, will be working with the infant and child cohorts. Her work will also address the difficulties of developing cognitive tests for infants and children with Down's syndrome and how to match these with the tests being developed for the mouse models.

The researchers hope that by bringing together such diverse disciplines, they will better understand the biology of Down's syndrome and how genes influence brain function throughout life in people with the condition. Ultimately, they hope this will lead to treatments that can be tested in clinical trials and can be used to halt the decline in brain function or even reverse the effects of Alzheimer's.

The research project addresses several of the Wellcome Trust's strategic challenges: maximising the health benefits of genetics and genomics; understanding the brain; and investigating development, ageing and chronic disease.

Dr John Williams, Head of Neuroscience and Mental Health at the Wellcome Trust, says: "The new research consortium is asking a very important and timely question: why people with Down's syndrome should also be at greater risk of developing Alzheimer's. We hope that by examining this link, the researchers will provide valuable insights into the neurodegenerative disorder which will benefit the patients themselves, but also offer hope to the many families who are affected by dementia in general."