Alzheimer's Disease is a progressive condition of brain cells degenerating, affecting up to 50 out of 1000 senior citizens from the age of 65 and older every year. Scientists recently discovered a gene within the brain that suppresses signs of Alzheimer's Disease.
Dementia is often the cause of Alzheimer's as brain cells degenerate, or waste away, and die. As an individual's way of thinking increasingly declines, the brain damage affects the person's ability to function normally.
When the disease infects the brain, symptoms include memory loss, becoming moody, inability to do menial tasks, and visual problems. To treat these cognitive symptoms, the U.S. Food and Drug Administration (FDA) has approved two types of drugs--memantine and cholinesterase inhibitors.
The study conducted by Queen Mary University of London analyzed the decline of brain cells and the observation of specific genes. They also created a new rapid drug-screening system for medication to prevent or delay the disease from developing.
A vulnerable set of people that risk developing Alzheimer's are those with Down syndrome (DS) due to their extra chromosome, carrying the gene for amyloid precursor protein. This protein gives DS individuals a 70% chance of developing the disease.
Conducting human trials of potential Alzheimer's drugs is challenging because those with symptoms have lost too many brain cells for the medication to make a significant difference. Instead, the team observed people with DS, who had a higher risk of developing the illness.
Suppressor Gene Protects Against Alzheimer's Disease
The scientists collected hair cells that were genetically re-engineered to become stem cells. The stem cells were then grown into brain organoids, or brain cells made in a laboratory dish.
Alzheimer-like activity was observed in the brain organoid, including amyloid plaque-like lesions, or damage. Simultaneous with the neuronal death, neurons were abnormally accumulating tau proteins--proteins that stabilize microtubules and have various functions in healthy brain cells.
Professor Dean Nizetic said, "this work represents a remarkable achievement, as 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."
His team developing a new rapid drug-screening system will allow other researchers to use the platform for early preventive drug testing. In their experiments, they used two drugs that inhibit amyloid protein production for six weeks. Their new system displayed how any drug compound can be assessed within six weeks for further studies or if it lacked potential.
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Suppressor Gene
In addition to their new system, they found proof of a natural Alzheimer suppressor gene called BACE2. It behaved in a similar way that tumor suppressor genes work against cancer cells.
An increase of BACE2 genes prevents and slows down Alzheimer's in brain cells, meaning that it may become a biomarker to determine which people have a high risk of developing the disease. New therapies may also be designed around the suppressor gene.
Nizetic explained, "Although it's still early days, the system raises a theoretical possibility for further development as a tool to predict who might develop Alzheimer's. The same stem cell process could be used on anyone's hair follicles, the resulting brain cells of which may or may not then develop Alzheimer's-pathology in the dish."
"The idea would be to catch the people at higher risk of early disease in a cell-based system, before it starts in a person's brain, and allow for the possibilities of individualized preventive interventions. We are still a long way from reaching this goal." 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."
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