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Alzheimer's Disease Genetics
Alzheimer's disease is a common type of dementia where the brain tissue degenerates. According to the Alzheimer's Society it affects 417,000 people in the UK. The exact cause of Alzheimer's disease is unknown at the present time, but it is strongly suspected that there are several factors involved such as age, inherited genes, diet, overall health, and environmental factors. If a family member has the disease an individual is at a higher risk than the average population. Though such genetic risk factors have been shown to be a problem in only a small number of families.
Genes that are thought to be involved in the cause and progression of Alzheimer's disease include presenilin-1 and the amyloid precursor protein gene on chromosome 21. Other chromosomes that are suspected of harbouring genes involved in Alzheimer's are 9,10 and 12. Clearly, it is a very complex situation.
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Alzheimer's Disease Stages
Alzheimer's disease is rare in younger people, but the risk does increase with age. The first stages tend to be forgetfulness, such as failing to remember or recognise familiar names, places, and events. Friends and family of an affected individual may notice a change in behaviour - a person with early stage Alzheimer's may become withdrawn, or frustrated at not being able to cope with the demands of life. As the brain deteriorates this memory loss can become more pronounced and the individual has difficulty learning new tasks, and may do things that are 'out of character.'
People with Alzheimer's can become disorientated easily, depressed and confused. In the later stages many don't recognise that they are ill at all and eventually Alzheimer's sufferers will become totally dependant on others. There may be difficulty with walking, urinary incontinence and speech difficulties.
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Genetic Engineering and Alzheimer's Disease
Although science is a long way off from finding a cure, genetic engineering could provide the answers.
Alzheimer's disease is caused by a loss of nerve cells. They die and cannot be replaced, and the brain shrinks. When the brain is in tip-top condition nerve cells send signals to other parts of the body in the form of electrical impulses. They are helped in this process by neurotransmitters such as acetylcholine. When nerve cells die there is not enough acetylcholine and it's believed that this impairs nerve cell transmission. And the accumulation of dead cells leads to the formation of harmful deposits, known as plaques.
How genetic engineering could help;
1) By using the body's immune system to fight back against the disease. In May 2008 University of Yale researchers published the results of their findings in mice bred to have dementia-like symptoms. The scientists used genetic engineering to block a particular immune system response in cells outside the brain. It resulted in defence cells known as macrophages entering the brain and getting rid of the plaques. In press interviews at the time one of the authors, Professor Richard Flavell, said: "It was like a vacuum cleaner had removed the plaques." The phenomenon of course has to be seen in humans if this particular avenue of research is to bear fruit. If so it could open the way for a drug to reproduce the effects.
2) Genetic engineering techniques in mice are revealing more about the progression of the disease and the consequences of therapeutic intervention. In 2006 researchers from Brigham and Women's Hospital and Harvard Medical School showed that the deletion of presenilin genes implicated in Alzheimer's caused memory loss and death of nerve cells. The genes contribute to the production of plaques and though plaque formation was reduced when the genes were not present in the mice models, the animals still went onto develop dementia and memory loss. The work is important because it suggests that any action or drug treatment that blocks presenilin genes could actually be detrimental.
3) Then there's the potential of gene therapy - replace the faulty genes with fully functioning ones. In 2005 there were reports that gene therapy trials delayed disease progression. It wasn't a cure, but the results were promising enough to merit further research. Scientists took skin cells from patients and modified them to secrete the protein nerve growth factor (NGF), which is present in healthy brains. These NGF producing cells had to be implanted directly into the injured parts of the brain and so doctors had to drill holes in the patients' skulls. They were tracked for almost two years after the operation and these patients showed that their cognitive decline was much slower than if they had been given medication.
Even though a genetic engineering cure for Alzheimer's is not here yet, and the precise molecular progression of the disease is unknown, there are grounds for cautious optimism as there are a number of different pathological features that are being pursued as targets for treatment.
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1) Inactivation of Alzheimer's Disease Genes in Mice Causes Dementia and Brain Degeneration - Bio-Medicine
2) Immune Block Tackles Alzheimer's - BBC News Online