BRAIN DYSFUNCTION DURING AGING: RELEVANCE FOR ALZHEIMER DISEASE

5.4 million people in the European Union currently have dementia and one in every 20 people over the age of 65 have Alzheimer’s disease (AD). Hence, AD is the most common cause of dementia among older people. Although current treatments can slow the progression of AD and help manage its symptoms in some people, there is no cure for this devastating disease. Furthermore, diagnosis is only clear when the affected individual presents symptoms that reflect irreversible brain damage, not in the earliest phases. If, to the human suffering, we add the social and economic cost of this disease (54 billion to the European social systems) it becomes evident that the solution will only come through a major effort from all governments and institutions to support research in this field.

It is important to appreciate that, although AD affects mostly old people, it is not a normal part of aging. In fact, one of the most important challenges in AD research is to define the causes by which normal aging becomes pathological. Most cases of AD cannot be explained by the occurrence of genetic mutations. However, in a large number of affected individuals it has been observed the existence of genetic alterations called single nucleotide polymorphisms, for which the relationship to disease is not clear. In other cases, environmental circumstances may also be the determinant. Yet, it is clear that the major predisposing factor is age. Hence, we will investigate whether or not and how genetic alterations and environmental events may tilt normal into pathological aging. Additionally, we will try to identify new genes that are responsible for normal aging and to which extent defects in such genes may lead to pathological aging. Finally, we will investigate in depth the molecular and biochemical basis of brain communications during normal aging, whether it is neuron-neuron communication, neuron-astrocyte or neuron-brain blood vessel, and how communication can be altered by genetic or environmental alterations leading to AD.

Success of this initiative will be the identification of common molecular pathways that are altered during aging leading to AD, irrespective of the genetic or environmental causes. Success will also be the identification of sets of genetic or environmental pathways. In either case the consequences will always be beneficial. First, because it will lead to the development of new molecular tools to identify the likelihood of developing AD before signs start and therefore initiate preventive measures. Secondly, because it will lead to the development of general or specific therapeutic tools.