Researchers identify genes linking early Alzheimer’s and Down syndrome

Researchers at The Francis Crick Institute have identified genes linked with early onset of Alzheimer’s disease in individuals with Down syndrome. The study published in Brain, has brought researchers closer to preventing Alzheimer in people having Down syndrome with future medicines and understanding the mechanisms behind dementia among general population.

In every 800 people, around 1 person is born with Down syndrome and around 2/3rd of the people having Down syndrome will have early onset Alzheimer’s by the time they are 60 years old or above.

Earlier it was thought that the high rates of Alzheimer’s in individuals with Down syndrome was due to a particular gene on chromosome 21 called APP. Chromosome 21 contains 231 genes. As APP produces amyloid precursor proteins, which are involved in generating amyloid beta proteins, building up in the brain in Alzheimer’s patients, APP was thought to be mainly responsible for Alzheimer’s in people with Down syndrome.




The researchers found that in a mouse model of Down syndrome extra copies of other genes on chromosome 21 increase Alzheimer’s-like brain pathology and cognitive impairments.

According to Senior Research Fellow and first author of the study Dr Frances Wiseman, his team of researchers has shown, for the first time that genes other than APP are playing a role in early onset Alzheimer’s disease in their model of Down syndrome. Understanding of these genes and the pathways involved in the earliest stages of neurodegeneration, could pave the way for future preventive intervention against Alzheimer’s in people with Down syndrome.

To identify the contributions of APP and other genes in Alzheimer’s disease, the researchers compared mice that produce APP amyloid protein with, and without, the presence of human chromosome 21. It was found that the mice having an extra copy of all the genes on chromosome 21 had more signs of Alzheimer’s disease than mice that had a single copy of the genes. Also, greater levels of amyloid beta were present in the mice that had extra copies of all genes on chromosome 21. These mice also had more clumps inside memory-controlling part of the brain and performed worse on memory tests. The researchers further found that the increased build-up of amyloid beta and clumps in the brain of these mice was caused by greater production of a particular type of amyloid beta protein that was more prone to forming clumps

According to Group Leader at the Institute and co-senior author of the paper Dr Victor Tybulewicz, Down syndrome had historically been very difficult to model in a mouse, and only after years of refining their mouse models, the earliest stages of Alzheimer’s, and other diseases, in the context of Down syndrome could be studied.

Elizabeth Fisher, Professor of Neurogenetics and co-senior author of the paper, told that although they were looking at Alzheimer’s disease through the lens of Down syndrome, this international collaboration provided insight into the earliest stages of disease progression, which might be applicable to modulating Alzheimer’s disease in the general population.

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