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Abstract:

Mouse models have been used in research about the pathogenesis and possible prevention or treatment of Alzheimer’s disease for more than 20 years already. The oldest models were based on pharmacological and surgical manipulations that related to the neurochemical and regional defects occurring in brains of Alzheimer’s disease patients. Recent models have focused on mimicking the pathobiochemical and histopathological features of Alzheimer’s dementia using techniques derived from molecular genetics. However, the validity of these mouse models eventually depends on the occurrence of functional defects that resemble the behavioral and cognitive defects in Alzheimer’s disease patients. This has challenged behavioral neuroscientists and comparative psychologists to develop tests and test batteries for reliable behavioral assessment in laboratory rodents in a methodological approach not dissimilar to diagnostic human neuropsychology. Tests of spatial learning and memory rank amongst the most complex behavioral tasks in rodents, and may be similar to declarative memory functions in humans. Other rodent cognitive tests include tests of behavioral flexibility, reversal learning, discrimination learning and multiple choice tasks. Several tests have been devised to assess emotional and social behaviors in lab rodents as well. Despite research efforts to improve the reliability and validity of rodent behavioral tests, the search for better and more relevant tests remains a major challenge in preclinical and translational Alzheimer’s research. It may even represent the major bottleneck in the slow progression and relatively limited translational success of therapeutic research and development in this field.