DW: Existing drug therapies for Alzheimer’s delay the progression of the disease only briefly. What benefits do the experimental drugs offer?

Prof. Beyreuther: Over the last five years, our understanding of Alzheimer’s treatment has changed dramatically. Once a large number of nerve cells have been damaged, therapy is no longer a viable option. That’s why the new drugs are being tested on patients in the early stages of the disease – when perhaps only 60 percent of the patient’s nerve cells have been damaged or destroyed. Currently the emphasis has also shifted away from trying to remove or eliminate amyloid plaques in favor of clearing the brain of the toxic buildup that heralds the preliminary stage of the disease. The new substances are designed to target and eliminate these soluble toxins, so that they don’t end up forming amyloid plaques. Studies have shown that these new substances do lead to a significant reduction of amyloid plaques in the brain, which can be observed using brain scanning techniques.

Do you believe this is an important breakthrough in Alzheimer’s research?

We’re very close to figuring out what actually causes the destruction of nerve cells in Alzheimer’s disease. Two U.S. pharmaceutical companies have built upon this research to develop two drugs, called solanezumab and aducanumab. However, these new drugs can only be used in the early stages of the disease. Once Alzheimer’s has progressed, cure becomes impossible. One of the reasons for my optimism is that aducanumab was created by investigating the antibodies present in an elderly donor who, despite being well over 90 years old, was cognitively normal with an immune system that appeared to have successfully resisted the development of plaques associated with Alzheimer’s disease. This drug is very promising. But both of these drugs are still in the experimental stage, and are not yet available on the market.

Of course, such treatments can only work when an early diagnosis has been obtained. If early diagnosis ends up being key, should we start offering medical examinations to everyone over a certain age?

As long as there’s no effective therapy, early diagnosis is only useful for research purposes, or to help affected individuals and families plan for the future. People who have first-degree relatives who died of genetic, early-onset Alzheimer’s disease at age 30, 40 or 50 might want to obtain an early diagnosis for family-planning purposes. But these individuals should also receive psychological counseling to help them cope in the event of a diagnosis. Once a therapy does exist, however, our existing technology will allow us to diagnose the disease approximately 20 or 30 years before symptoms become apparent. However, not all of these people will actually end up suffering from Alzheimer’s – even with a negative prognosis, some people never develop the disease. We still don’t know why that’s the case. But we advise patients to only seek a diagnosis when the first signs of cognitive decline become apparent. That’s about five years before the first real symptoms become apparent, and nowadays our diagnostic techniques are quite reliable at that stage of the disease.

Does Alzheimer’s disease have a genetic component, and do people from such families have a higher risk of suffering from the disease?

There are two general hereditary factors that play a role in Alzheimer’s disease. One involves genetic mutations that cause the disease to appear at a young age, generally before age 60. And then there are genetic risk factors that predispose the development of the disease. About half of all Alzheimer’s patients are affected by a risk factor associated with cholesterol levels. But we know today that this particular genetic risk factor only becomes relevant if the patient suffers from high blood pressure in middle age. If the patient has normal blood pressure, this particular risk factor doesn’t lead to an increased rate of Alzheimer’s disease. There are about 20 other known risk factors that can affect the early stages of the disease, or cause Alzheimer’s to appear at a younger age. Most of these risk factors can be ameliorated by lifestyle changes or a reduction in non-specific risk factors. For families that display several of these risk factors, this can also result in Alzheimer’s diagnosis at a younger age. And then you have other individuals who don’t develop Alzheimer’s because they have a good immune system. So if your parents reached the age of 90 without developing Alzheimer’s, there’s a good chance that you’ll be fortunate in this respect as well. Once we have effective therapies, however, then individuals with parents who died of Alzheimer’s between age 60 and 70 might want to consider early diagnosis.

What risk factors promote the development of Alzheimer’s disease?

There are seven risk factors that are affected by lifestyle, which together account for about half the risk of developing Alzheimer’s disease. The other half of the risk is due to genetic factors. The seven lifestyle-associated risk factors are very interesting, because those are risk factors over which we have some influence. The main lifestyle-associated risk factor is depression, for which we have effective treatments. The second-most important of these risk factors is a sedentary lifestyle. Our recommendation is that everyone walks at least 10,000 steps per day. The third risk factor is high blood pressure during middle age. By old age, high blood pressure is no longer a risk factor, since Alzheimer’s disease takes 30 years to develop. The fourth risk factor is overweight during middle age. It’s growing increasingly apparent that being overweight is a very significant risk factor. The other lifestyle-associated risk factors are lack of mental activity, smoking and diabetes. Recent research has suggested that diabetes can lead to low blood sugar levels in the brain, which is a significant risk factor for Alzheimer’s disease.

Is there anything we can do to prevent Alzheimer’s disease, or at least slow the progression of the disease?

It is possible to slow the progression of the disease. For example, the brain is a major consumer of energy. One-quarter of our body’s energy is consumed by the brain. This metabolic process gives rise to aggressive oxygen molecules, or free radicals. That’s why it’s best to consume a diet rich in fruit and vegetables – with an emphasis on vegetables, because the fructose in fruit can be problematic. Nerve cells benefit from plant substances as well as fish oil and omega-3 oils, which also benefit the heart. In addition, it’s also helpful to keep the brain active in other ways, for example with music, which stimulates the brain in special ways. Physical activity is also helpful, especially when it promotes the establishment of time and spatial representations encoded in the brain’s place cells, which promotes biographical memory. In addition, stress management and sufficient sleep are very important. The brain needs rest phases in order to process the day’s events.

It’s said that the number of Alzheimer’s patient will triple by 2050. Do you believe that current research supports that projection?

No one can predict the future, but I suspect that the number of Alzheimer’s patients will stay at current levels rather than rising worldwide. I do think the number could rise slightly, simply because of world population growth. But in our digital age, people are much more health-aware, and they are paying more attention to blood pressure, weight, cholesterol levels, physical activity, and an overall healthy lifestyle. That’s one reason why we’ve seen a decline of about 20 to 25 percent in new diagnoses in some northern European countries. However, improved medical care has also extended the lifespan of Alzheimer’s patients in those countries, which means that the overall number of patients has not declined appreciably. It’s still too early to say how developing countries will be affected, but these countries are also experiencing a rise in educational levels and health awareness gleaned from online sources. So our digital society appears to be leading to a reduction in Alzheimer’s rates, and later disease onset. So I don’t personally believe that we’ll see a tripling of Alzheimer’s patients by 2050.

Professor Konrad Beyreuther is a molecular biologist at the University of Heidelberg and one of the world’s leading Alzheimer’s researchers. He played a key role in the discovery of the chemical structure and genetic aspects of the amyloid plaques that are characteristic of Alzheimer’s disease, and has received numerous awards for his work. He is also the founding director of the Network Aging Research at the University of Heidelberg.

http://www.nar.uni-heidelberg.de

Interview: Marita Brinkmann