DEMENTIA: GENETIC AS ONE OF THE THEORIES

There have always been some cases of Alzheimer’s disease that have appeared to run in families. The most well researched ones have been found where the condition has occurred in younger people (like the original cases Alzheimer described). We know however that this type of dementia in younger people is very rare (0.1 per cent of total cases of dementia). There are in fact only 12 families world wide currently being studied with this rare and obviously directly inherited form of the disease. In studying these families it did seem that the condition was passed on to the next generation but not in a very straightforward pattern – one could not predict which offspring if any would develop dementia. We now know that Alzheimer’s disease becomes much more common as we get older (as high as 20 per cent of the over-80 age group is affected). Being quite common, it then becomes hard to know if the dementia is passed on in a family or whether or not the dementia has occurred in the next generation by chance; one has to wait for the children to grow old, and they have a 20 per cent chance of developing dementia anyway.
Someone then noticed that all cases of Down’s syndrome developed a condition identical to Alzheimer’s disease before they died young. It had been recognized for a long time that people suffering from Down’s syndrome ‘aged’ very quickly, but it was not until this observation about their dementia was made that its importance was realized. Studies on the brains of people dying with Down’s syndrome show all the changes seen in those dying with Alzheimer’s disease. Now, we don’t know what causes Alzheimer’s disease but we do know the cause of Down’s syndrome; in the majority of cases it is due to a fault in the chromosomes, the tiny bits of genetic material that are found in each cell and that originally come from each parent.
Each of us has 23 pairs of chromosomes, 46 chromosomes in all, in each cell. The only exceptions are sperm cells in men and ova (the egg cells) in women – they have 23 single chromosomes, half the usual number. When a baby is conceived by the fusion of a sperm and an ovum, the full complement of 23 pairs of chromosomes is achieved, the baby’s cells containing a mixture of the mother’s and father’s chromosomes. In a Down’s syndrome baby something goes wrong with this process and chromosome pair number 21 ends up with an extra bit of genetic material. This tiny excess produces all the abnormalities associated with the condition, including the development of changes exactly like Alzheimer’s disease. Each chromosome is made up of hundreds of genes (small sequences of genetic information controlling a bit of the workings of the body). It seems likely therefore that as chromosome 21 has the gene that produces Alzheimer’s disease in Down’s syndrome, the same chromosome should have a gene for Alzheimer’s disease in non-Down’s-syndrome people with, or who will develop, Alzheimer’s disease.
The topic is made more complicated by the finding that chromosome 21 may not be the only genetic source of the problem. Researchers have found families with early onset dementia where chromosome 14 is abnormal and some where chromosome 19 is probably at fault. Many researchers now feel that these genetic changes are more important than the original lead with chromosome 21 and Down’s syndrome, which may have given the impetus but will not be the answer. In addition medical interest is now focusing upon the role of a protein in the body called amyloid – more specifically beta-amyloid. The amyloid is governed by the amyloid APP gene and this abnormality also appears to run in families, making it another familial form. It appears that some cases of dementia are caused by a gene for the precursor stage of beta-amyloid being in the wrong place causing this protein to be abnormally deposited all over the brain. What is unknown is the relative significance of these findings and how important to the general population are the findings of an abnormal chromosome 21, chromosome 14 and the misplaced gene for beta-amyloid (and even if the beta-amyloid gene is related to the other chromosomal abnormalities and in what way).
Finding a gene on a chromosome may sound easy but in fact it is extremely difficult. Researchers in both the UK and the USA are currently working on this project and they expect to be able to identify the gene soon. This will then open up many more research possibilities. Once identified it can be looked for in people currently suffering from Alzheimer’s disease. Is it present in every case? If not, do those who appear to have Alzheimer’s disease but who do not have the gene really have Alzheimer’s disease, and not some other similar condition? Is the gene passed from generation to generation? If present in normal healthy people, will they go on to develop the disease? As you can see it is exciting research but it throws up many difficult questions. Should you look for and tell someone they are carrying a gene that may mean that they develop dementia, a condition for which there is currently no cure?
Most of the experts working in this field think it is unlikely that carrying the gene alone will automatically mean that the person will develop dementia, unless they are in one of those families where the disease presents very early. It is felt that the gene being present means that you are more at risk than someone without the gene, but that you still need a trigger to set the whole thing off. More and more attention is being paid to environmental triggers – abnormalities in the environment which can act as general hazards – the theory being that such triggers, when put together with a genetically predisposed individual, result in dementia developing.
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