A gene has been discovered that can naturally suppress the signs of Alzheimer's Disease in human brain cells and based on it, scientists have developed a new rapid drug-screening system for treatments that could potentially delay or prevent the disease.
The main challenge in Alzheimer's drugs is testing as once people have symptoms, it is usually too late for treatments, as many brain cells have already died.
The only current way to drugs is by identifying participants who are at higher risk of developing Alzheimer's and seeing if treatments prevent the onset of their disease. This includes people with Down's syndrome (DS) who have around a 70% chance of developing Alzheimer's during their lifetime. This is because the extra chromosome 21 they carry includes the gene for amyloid precursor protein which causes early Alzheimer's when overdosed or mutated.
Down Syndrome hair cells
The findings by Queen Mary University of London was published in the Nature group journal Molecular Psychiatry. The team of researchers collected hair cells from people with DS and reprogrammed them to become stem cells, which were then directed to turn into brain cells in a dish.
They found Alzheimer's-like pathology develop rapidly, including the hallmark trio of signs of Alzheimer's progression - amyloid plaque-like lesions, progressive neuronal death and abnormal accumulations of a protein called tau inside neurons.
Lead researcher Professor Dean Nizetic from Queen Mary University of London said, "This is the first cell-based system that has the full trio of Alzheimer's-pathologies, without any artificial gene overexpression. This system opens up the prospect for screening for new drugs aimed at delaying or even preventing Alzheimer's before neuronal death starts."
The researchers said the system could be used as an early preventative-drug testing platform. They tested two different drugs which are known to inhibit β-amyloid production on these brain cells, and in six weeks they prevented the onset of Alzheimer's-pathology.
Although these two particular drugs have failed clinical trials for other reasons, the team showed the proof-of-principle that the system can be used on any drug compound, and within six weeks show whether or not it has potential for further investigation.
The team also found proof of the existence of a naturally-functioning Alzheimer's suppressor gene (BACE2 gene). Acting in a similar way to tumour suppressor genes in cancer, the increased activity of this gene contributes to the prevention/slowing down of Alzheimer's in human brain tissue. Hence, this could in the future be used as a biomarker to determine people's risk of developing the disease, said researchers.
Co-author Professor John Hardy from UCL said, "I think we have the potential now to develop a new, human model of the disease which would be a great step forward."