The modified amyloid hypothesis of Alzheimer dementia - intraneuronal Abeta induces neurodegeneration

Abstract

The present short review recapitulates the molecular pathology of Alzheimer's disease and discusses the most important animal models and current treatment strategies. The currently approved and only mildly efficient drugs treat only symptoms. Genetical, neuropathological and biochemical data support the importance of the amyloid hypothesis of Alzheimer's disease, which is at the moment the most influential hypothesis. The resulting research approaches have disease-modifying potential. At the basis of the amlyloid hypothesis many treatment strategies have been performed, which were markedly successful in preclinical animal models. However, the treatment success in Alzheimer patients is unfortunately still lacking. This could be due to the used animal models showing mostly only marginal behavioural deficits and no Alzheimer-like nerve cell loss, although they all developed a more or less pronounced plaque load. We know however today, that Alzheimer plaques are not mainly responsible for the cell loss. Therefore novel animal models have been developed that show early intraneuronal A beta accumulation, massive neuron loss and robust behavioural deficits. A successful treatment of an animal model with such a phenotype would be very likely better suited to be transferred into the clinic. The final validation or falsification of distinct Alzheimer hypotheses and the resulting treatment strategies will be obtained however only after clinical proof.