14 April 2009
Science Communications Officer, the Alzheimer's Research TrustAppeared in BioNews 503
It has been known for 15 years that the APOEe4 gene variant is a risk factor for late onset Alzheimer's disease. The APOE gene exists in several forms (e2, e3 and e4) - and large population studies have shown that the e4 variant increases a person's risk of developing the condition (2). However, the APOEe4 variant is common - a quarter of the UK population have at least one copy - and most people with it will not develop Alzheimer's disease. Equally, many people with Alzheimer's disease do not have the APOEe4 gene. Alzheimer's disease is a complex disease not fully understood, with many interacting causes, both genetic and environmental. Knowing whether someone has the APOEe4 gene is not, therefore, an accurate predictor of their risk of developing the disease.
In the recently reported study, researchers looked at the difference in brain activity between two groups of healthy young people, half (18) of which had the APOEe4 gene (3). The researchers used fMRI to study brain activity in the two groups when they were performing memory tasks and when they were at rest. They found distinct patterns: those with APOEe4 had greater activation in areas of the brain involved in memory formation than those without. This difference was seen even when the participants were not doing any memory tasks. They hypothesise that APOEe4 can modulate brain function decades before any clinical or physiological expression of neurodegeneration appears.
To determine whether the activation seen in this study has any bearing on a person's risk of developing disease, the participants need to be studied over a long time period. At the moment, the results do not help us to differentiate e4 carriers who will go on to develop Alzheimer's disease from those who will not. It does pave the way for further studies that could help us understand how brain function in younger adults may contribute to the development of Alzheimer's disease later in life.
Each new piece of work like this brings scientists closer to understanding what is happening in the brain as we age, and how it can go wrong in neurodegenerative disease. Increasing public awareness of dementia has brought the disease into the spotlight, and people are willing to speak out about a disease that was once hidden in the shadows. Much more work needs to be done to discover the risk factors and causes of dementia. Further research will likely lead to ways to prevent and treat it.
At the moment, Alzheimer's disease is difficult to diagnose. Diagnosis involves ruling out other causes of symptoms and can only be confirmed post-mortem by looking at the 'plaques' and 'tangles' of proteins that are the pathological hallmarks of the disease. An accurate diagnostic test is desperately needed. Many researchers believe that the disease process starts 10-15 years before any clinical symptoms appear. This is the time then, when treatments are likely to be the most effective and therefore clinicians need to be able to identify those people that need them.
At the moment effective treatments are not available, while current treatments halt only some symptoms for a time. It is not all doom and gloom however; there are about 13 drugs in phase three clinical trials that aim to slow down or halt the progression of the disease. If just one of these is successful and can prevent the onset of the disease by just five years, the number of people dying with Alzheimer's disease will halve.
Research is building up an ever more accurate picture of dementia, and hopefully will lead us to the answers we need. The number of people with dementia is expected to reach 120 million globally by 2050 (4), and treatments have never been more urgently needed.