Animal models in the development of symptomatic and preventive drug therapies for Alzheimer's disease

Abstract

Dementia of the Alzheimer type (AD) is clinically characterized by a progressive deterioration of intellect, memory, judgment, and abstract thinking. It is incurable, and causal therapy is not yet available. For the development of therapeutic drugs, valid animal models are needed that mimic the pathophysiological change in brain functions and the concomitant behavioural deterioration seen in AD patients. This article provides an overview of the animal models that are used most often to study the substrates and mechanisms of the pathological changes underlying AD and to identify, characterize and develop putative neuroprotective, antidegenerative, revalidation-supporting and/or cognition-enhancing compounds or treatments. The first generation of agents for the symptomatic treatment of the disease has been developed on the basis of results obtained with these models. These drugs are presently undergoing clinical testing or are already used therapeutically. There is, however, no single animal model that can mimic the full range of pathophysiological alterations and key symptoms of AD. New, genetically engineered mouse models that mimic at least some of the key pathological changes of AD are expected to provide tools that will facilitate the development of symptomatic and preventive drug therapies.

Key Words:

• animal model
• Alzheimer's disease
• amyloid precursor protein gene (APP)
• drug administration schedules
• learning
• memory
• rat
• transgenic mouse
• validity