Project
Functional parameters that depend on prefrontal cortex and hippocampus in mouse Alzheimer's disease models and their use to evaluate experimental therapies.
Memory and learning are cognitive processes at the core of our humanity. There are almost 30 million people worldwide suffering from Alzheimer's disease (AD), a number that is expected to quadruple by 2050. Presently approved drugs and cognitive rehabilitation therapy merely address some of the symptoms. More than ever, there is a need to support fundamental AD research in its various multidisciplinary forms. However, biopsychological approaches (in comparison to molecular, pathobiochemical and biomedical ones) are much less common in this field, even though the importance of functional and neurobehavioral observations in AD animal models is widely recognized. In this project, we will investigate the sensitivity of psychometric and metaplasticity parameters that depend on the prefrontal cortex and hippocampus and the interaction of these regions, to evaluate the treatment of characteristic AD symptoms in two established mouse AD models that display either the characteristic amyloid-β plaques (i.e., APP/PS1 mice), or neurofibrillary tangles (i.e., tau22 mice). AD mouse models have become indispensable to probe into mechanisms of AD and test new ways of treatment. Thus, we will combine measures of metaplasticity and general cognitive ability to investigate the validity of these putative AD models and their responsiveness to experimental therapeutics. We have selected three different approaches that relate to leading hypotheses about AD pathogenesis (i.e., enzyme inhibitors, nutritional trace element, endogenous compound with proven effects on growth factors).