Prof. Dr. Dr. h.c. Konrad Beyreuther
Interview of March 21, 2007 with Dr. Birgit Teichmann
First of all, we would like to know from you, as a specialist for Alzheimer, if research has made any progress in regard to the treatment of Alzheimer Dementia.
We have been working since 25 years on the molecules, which are involved key players in Alzheimer disease. After these 25 years I can firmly state that we have advanced enormously. This advance is based mainly on the thorough understanding of the processes that destroy the human brain in Alzheimer‘s disease. These results allowed the scientific community to produce animal models, which develop the characteristic ß-amyloid protein deposits, the patholgical hallmarks of Alzheimer‘s disease. These animal models greatly helped to advance our ideas about biologicial markers suitable for the diagnosis of Alzheimer‘s disease and therapies suitable to slow down or stop disease progression, which we first developed in cell cultures or in the test tube.
It is believed that early diagnosis of the disease improves the chance to slow down the disease process. Are there any markers suitable for an early diagnosis of Alzheimer‘s disease ?
Early diagnosis of the disease is indeed one of the most important issues, which we have to concentrate on for the following reason. The disease progresses in three phases, each with an average duration of three years. Already in its first mild stage, 70 per cent of the nerve cells responsible for memory are damaged. In the following two stages, moderate and severe Alzheimer‘s disease, already 90 per cent and more than 90 per cent of these nerve cells, respectively, are damaged. There is no therapy for an empty brain! That means we have to diagnose as early as possible in order to be able to intervene at the time of mild cognitive impairment (MCI). About 70 per cent of the individuals who were diagnosed as MCI developed Alzheimer‘s disease- at the latest after 5 years. To secure this difficult early diagnosis, a biological test based on ß-amyloid has been developed, which is now waiting to be used. By the way, every clinical trial I am aware of which aimed to slow down or halt disease progression was only successful with MCI patients. Obviously, there it is not to late!
What medication is presently on the market, which will avoid or reduce the ß-amyloid protein deposits in the brain of patients with Alzheimer‘s disease?
At present, more than 100 compounds that were developed to slow down or even stop the disease process are tested in clinical and preclinical trials. At the moment already four substances are available for treatment, all of which improve the quality of life of the patients and caregivers, but cannot modify the disease.
There are a number of medicines prescribed for other disorders, which also look promising for the treatment of Alzheimer‘s disease. Among these are cholesterol synthesis inhibitors of the statin type, anti inflammatory drugs such as indomethacin, heparin mimetica and micronutrients such as folic acid and omega-3-fatty acids such as docosahexaenoic acid (DHA). DHA is a constituent of fish oil.
New vaccines are applied to an increasing number of disorders; recent success is a vaccine against cervix cancer. A vaccine against Alzheimer has been announced by the press, but with severe side effects. What about an Alzheimer vaccine with fewer side effects?
Many Alzheimer researchers look at the Alzheimer vaccine approach as a possible break-through. Recently, I attended an international congress with over 2000 Alzheimer and Parkinson researchers. One of the topics was immune therapy, vaccination against Alzheimer‘s disease. In principle, there are two different vaccination approaches, active and the passive immune therapy. Active vaccination means that the patient is producing the antibodies, whereas in the case of passive vaccination the antibodies are injected directly into the patient. The latter is very expensive since it requires highly purified antibody preparations, which are very expensive to produce. With the present knowledge, both vaccination procedures may lead to complications such as bleedings (cerebral haemorrhages) or brain infections (encephalitis). Both adverse reactions may only affect a small number of patients. These patients at risk must be identified if vaccination is going to be widely used. To identify these patients is only a matter of time since the causes of the complications are known.
What can each individual do to avoid the disease or at least slow down the Alzheimer process before disease symptoms occur? You mentioned the Omega-3-fatty acids. Who eats fish or sea fruit, at least once a week, reduces his risk for Alzheimer.
The life style plays a major role for all age-associated diseases, including Alzheimer‘s disease. Mental fitness displayed by a life long learning process (interest in novel information) is as vital as supplying the brain with its important micronutrients. Most patients with Alzheimer‘s disease have reduced levels of folic acid, which is indispensable for learning, and not enough Omega-3 fatty acids, especially DHA. Omega-3 fatty acids are very important for the brain. They are typically found in vegetable oils such as linseed oil, rapeseed oil and all nut oils. The best source is fish oil, which contains high amount of DHA. A clinical study from Sweden, published in October 2006, seems to confirm this. The progression of Alzheimer‘s disease was slowed down in MCI patients, who took daily 2,3 g of the Fish oil components DHA (1,7 g) and eicosapataenoic acid (EPA) (0.6 g). Recently, a much larger study with five hundred MCI patients has been initiated by the National Institute of Aging of the US. This study has the power to show whether the Swedish study with its 32 patients can be replicated in a much larger number of patients that reach statistic significance.
Today approximately 1,5 Mio people in Germany are suffering from Dementia, 1,2 Million alone from Alzheimer‘s disease. Due to the steadily increase in life expectancy, it is suggested that by the year of 2050 the number of individuals with Dementia will be two to two and a half times higher than today. How do you see these numbers?
The number of Alzheimer patients in Germany can only be guessed, because it is diagnosed at late stages, if at all. There are different reasons for that. The patients and their family members are afraid to learn of the diagnosis and the physician is afraid to lose his patient when he diagnosis Alzheimer‘s disease. If I take as basis the somewhat reliable American statistics, Germany has about 1,2 Million Alzheimer patients, not including the 3-400 thousand MCI patients. You are right, this number will at least double by the year 2050. The reason for this is the increasing life expectancy – mean age at death - according to the prediction of the statisticians from today's viewpoint.
But to be honest, as an experimental researcher, I do not believe that this is indeed the case. As already mentioned, we have already data from animal experiments how Alzheimer‘s disease pathology can be postponed. In addition, until 2050 we will know which of the by then wide over 100 medical substances can be used to slow down or halt the process driving Alzheimer‘s disease. I think it is highly likely that the number of Alzheimer patients in Germany, 50 years from now, shall be lower than today. However, we have to invest more money than today into basic research on Alzheimer‘s disease and equally important, into aging research if we want to achieve such a goal, provided we are willing to invest intensively in the research on Alzheimer‘s disease and aging.
You are the Founding Director of the NAR, Network Aging Research. The NAR is combining researchers in the field of biology, medicine, sociology and economy. What do you expect with regard to the research on Alzheimer from this cooperation?
It is fascinating for me that aging is hard to define. People are aging differently, the process of aging cannot be measured yet and therefore diseases, defined as age associated, are used to study aging. I am sure this is legitimate, but age is not necessarily identical with disease. It is the sum of damages which life leaves in our bodies. It has been demonstrated that nearly all processes running in a cell to maintain its living show weaknesses, errors occur and on a long term do not proceed with the necessary perfection. I believe that a detailed knowledge of these weaknesses and what is required for a cell to maintain its integrity can contribute to a better understanding of the aging process. For this we need the expertise of molecular biologists and cell biologists. Heidelberg is known for his excellence in these fields and that’s why I believe Heidelberg is the right place for establishing the NAR.
At present, I try to bring together all researchers, who can contribute substantially to the understanding of the many aspects of aging, the biologists and clinical researchers, the sociologists and gerontologists around Profs. Kruse and Wahl, the epidemiologists around Prof. Brenner and the economists around Prof. Börsch-Supan. My impression is that we are already on the way to become a world center of aging research.
And how can the citizen profit from this?
Basic science is very expensive and needs tax payer’s money. This has to be explained to the people, in that you tell them how they benefit. Aging research shows clearly that each one of us has a responsibility towards his own body and genes. This responsibility can only be exercised when we are educated and informed on the latest research results. To achieve this, the Network Aging Research plans to establish a Fellowship Program in which young and more senior scientists work together and serve as translator who passes on research results to the public. I consider this as one of the prime responsibilities of the Network towards the community.
Konrad Beyreuther, born in 1941, Director, Researcher and "Bundesverdienstkreuzträger", member of the Heidelberg Academy of Sciences and Humanities and the German Academy of Sciences Leopoldina, member of the State Council of Baden-Württemberg from February 2001 until June 2006. He was decisively involved in the discovery of the chemical structure of the characterictic Amyloid-deposits of the Alzheimer disease and its genes. Beyreuther received numerous honours, the latest being the "Lennox K. Black International Prize for Excellence in medicine" of the Thomas Jefferson University of Philadelphia in collaboration with Colin L. Masters, University of Melbourne.
Mental and physical fitness, a continuous curiosity, as well as a balanced diet, rich on vitamins and Omega-3 folic acids - without neglecting enjoyment - is in his opinion the best prevention.
He is connected to the music festival "Heidelberger Frühling" as the chairman of their "Freundeskreis".