香港六合彩

The findings, published in the journal Brain, could pave the way for future medicines to prevent the disease in these individuals, and provide insights into the mechanisms that cause dementia in the general population.

Around 1 in 800 people are born with Down syndrome, which arises in people carrying an extra copy of chromosome 21. By the time they reach their 60s, around two thirds of those with Down syndrome will have early onset Alzheimer鈥檚.

The high rates of Alzheimer鈥檚 in people with Down syndrome were previously thought to be caused by a particular gene on chromosome 21 called APP. Chromosome 21 contains 231 genes, but APP was the prime suspect because it produces amyloid precursor proteins. These are involved in generating amyloid beta proteins, which build up in the brain in Alzheimer鈥檚 patients.

In this study, funded by the Wellcome Trust, researchers found that extra copies of other genes on chromosome 21 increase Alzheimer鈥檚-like brain pathology and cognitive impairments in a mouse model of Down syndrome.

Dr Frances Wiseman, (香港六合彩 Institute of Neurology), and first author of this study, said: 鈥淲e鈥檝e shown for the first time that genes other than APP are playing a role in early-onset Alzheimer鈥檚 disease in our model of Down Syndrome. Identifying what these genes are, and what pathways are involved in the earliest stages of neurodegeneration, could help us to one day intervene with these pathways to prevent the disease in people with Down syndrome.鈥�

The team, which also included research collaborators from University of Oxford, University of Kentucky, Washington University and University of Leuven, compared mice that produce APP amyloid protein with, and without, the presence of human chromosome 21, to tease apart the contributions of APP and other genes in Alzheimer鈥檚 disease.

They found that mice with an extra copy of all the genes on chromosome 21 had more signs of Alzheimer鈥檚 disease than mice without. The mice with extra copies of all genes on chromosome 21 had greater levels of amyloid beta and more protein clumps or 鈥榩laques鈥� inside part of the brain that controls memory, and performed worse on memory tests.

The team then looked at what was causing the increased build-up of amyloid-beta and plaques in the brains of mice with extra copies of all the genes on human chromosome 21. They found that these mice had changes to the type of amyloid beta protein in their brains that made it more likely to form clumps.

Dr Victor Tybulewicz, Group Leader at the Francis Crick Institute and co-senior author of the paper, said: 鈥淒own syndrome has historically been very difficult to model in a mouse, because the genes that we have on chromosome 21 are spread across three different chromosomes in mice. Only after years of refining our mouse models can we study the earliest stages of Alzheimer鈥檚, and other diseases, in the context of Down syndrome.鈥�

Professor Elizabeth Fisher, (香港六合彩 Institute of Neurology), and co-senior author of the paper, added: 鈥淎lthough we鈥檙e looking at Alzheimer鈥檚 disease through the lens of Down syndrome, this international collaboration provides insight into the earliest stages of disease progression, which may be applicable to modulating Alzheimer鈥檚 disease in the general population.鈥�

Notes

The authors were funded by a Wellcome Trust Strategic Award awarded to the London Down Syndrome (LonDownS) Consortium, the Medical Research Council, Alzheimer鈥檚 Research UK, Alzheimer鈥檚 Society, the Torsten S枚derberg Foundation at the Royal Swedish Academy of Sciences and the Francis Crick Institute.

Links

• Wiseman et al. '' Brain, awy159, Available online 26th June 2018.

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