Mechanisms underlying protein tau-mediated neurodegeneration: combining transgenic mouse models and AAV vectors.

Fundamental and translational data from clinical and pre-clinical research in Alzheimer's dementia (AD)support the hypothesis that amyloid is the "trigger" both in familial and sporadic AD, but that tauopathy is the actual "executer". The study of the role of protein tau and of tauopathie in brain and in AD is absolutely essential, both for academic as for diagnostic and therapeutic reasons. We test the working hypothesis in this project and aim at select aspects and important questions that link physiology and pathology: (i) what is the role of GSK3alfa/beta isozymes and their activation by amyloid? (ii) what is the role of protein tau in cognition and in neuronal cell-death? (iii) what post-translational modifciation(s)of protein tau are in vivo important for normal dendritic spines & synapses? (iv) what relates Tau-mediated neurodegeneration to microglial activation? We combine transgenic and viral models, multi-disciplinary analysis and pharmacological approaches to dissect the different mechanisms that contribute to normal neuronal function and to the neuronal damage in Alzheimer's disease.

Keywords:In vivo, Tau, Alzheimer's disease, Neurodegeneration, Nueroinflammation, Adeno-associated virus, Transgenic mice, GSK3

Disciplines:Laboratory medicine, Medical systems biology, Molecular and cell biology, Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing, Genetics, Systems biology