Is Alzheimer's disease curable?

From: Alzheimer Info 4/12

New approaches to the therapy of Alzheimer's disease

The currently available drug therapy methods and those in development start at different points in the disease process and pursue different goals. Conventional drugs try to compensate for the consequences of nerve cell death. They are used in the stage of dementia. The new pharmacological strategies aim to slow down the death of nerve cells. Their use is particularly promising in the disease stage that precedes dementia.

Mild cognitive disorder and dementia are different stages of the disease

The symptoms of Alzheimer's disease are caused by a gradual deterioration of nerve cells and nerve cell contacts. This process begins in the depth of the temporal lobe and remains clinically silent for many years. When it reaches the hippocampus, a structure of the brain that is particularly important for memory, the first symptoms appear in the form of increasing forgetfulness. Initially, it does not cause any significant restriction in everyday activities. This stage of the disease is known as "mild cognitive disorder". When the disease process spreads to the adjacent sections of the cerebral cortex, other symptoms appear in addition to the impaired memory and the activities of daily living are impeded. This condition is called "dementia".

The genesis of Alzheimer's disease

The most widespread theory about the development of Alzheimer's disease places the increased formation, clumping and deposition of a small protein (beta-amyloid) at the center of the pathological process. An imbalance between the production, breakdown and removal of amyloid leads to an increased concentration of this protein in the brain. Small amyloid complexes are formed which have a damaging effect on nerve cells and nerve cell contacts. The small complexes gradually develop into larger deposits, the plaques. In the nerve cells damaged by amyloid, another protein (dew) aggregates to form the characteristic neurofibril bundles. They impair important metabolic processes and contribute to the destruction of nerve cells and nerve cell contacts.

How the current drugs work

The drugs currently used to treat Alzheimer's disease (antidementia drugs) have no influence on the processes mentioned. They correct changes in transmitter substances that are a result of nerve cell death. This will delay the increase in symptoms by several months. The cholinesterase inhibitors donepezil, galantamine and rivastigmine (trade names: Aricept, Reminyl and Exelon) compensate for the deficiency in the carrier substance acetylcholine, which is important for memory and attention. The glutamate receptor antagonist Memantine (trade names: Axura, Ebixa) improves signal transmission between nerve cells in the cerebral cortex. The effectiveness of these drugs has only been proven for people with dementia. They can therefore only be used when the disease process is already well advanced and those affected have lost a large part of their cognitive performance and everyday skills.

New approaches to treatment

New treatment approaches have been tried out for several years. Its aim is to influence the processes that contribute to the destruction of nerve cells and nerve cell contacts in order to slow down the disease process itself. Some of the tested active ingredients inhibit the enzymes involved in the production of amyloid (secretase blockers), others prevent the agglomeration and deposition of amyloid (aggregation inhibitors). Various strategies are used to try to dissolve any amyloid deposits that have already formed. They make use of the immune system that is also present in the brain, either through the administration of antibodies that recognize the amyloid and the body's own defense against it (passive immunization), or through the administration of synthetic amyloid fragments, which enable the formation of stimulate specific antibodies and in this way also mobilize the body's own defenses (active immunization). In addition to strategies related to amyloid, treatment options are also being investigated which are intended to prevent or reverse the accumulation of tau and thereby influence the course of the disease process.

It was recently announced that antibody therapy directed against amyloid with the test substance bapineuzumab in patients with mild to moderate Alzheimer's disease had not achieved the treatment goals set. On the other hand, there is evidence that therapy with the antibody solanezumab is able to delay the course of the disease. If this result is confirmed, a form of treatment would be found for the first time that attacks a central mechanism of the disease and achieves clinically significant effects. In this case, the future aim will be to recognize Alzheimer's disease at a stage in which those affected have numerous cognitive abilities and everyday skills, and to ensure that they cope with the state of dementia and the associated with it through early therapy associated need for long-term care significantly later or possibly not at all.

Dr. Timo Grimmer
Clinic and Polyclinic for Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technical University of Munich