CO-EXPRESSION OF VIRALLY INDUCED P301L TAU AND TRANSGENIC BETA-AMYLOID IN APP MICE AS MODEL OF ALZHEIMER’S DISEASE TO MORE CLOSELY MIMIC HUMAN PATHOLOGY

Alzheimer’s Disease (AD) is the most common neurodegenerative disorder worldwide causing dementia in aged people. Brains from AD patients are characterized by two main pathological hallmarks: (1) Neurofibrillary tangles (NFT) consisting of hyperphosphorylated Tau aggregates, and (2) senile plaques comprising insoluble β-amyloid (Aβ). Thus a mouse model co-producing both pathological Aβ and Tau would be a well suitable model to mimic AD. To generate such a model we for the first time virally induced Tau expression with the most prevailing mutation in various types of dementia, P301L human Tau, in the hippocampus of APPSL transgenic mice by stereotactic injection. Biochemical and histological analyses revealed stable expression of P301L Tau in the hippocampus and the cortex for several months after injection. Furthermore, we detected increased levels of hyperphosphorylated Tau in the same brain regions. Ongoing experiments aim at a thorough molecular and behavioral characterization of these mice. Together, we show that our inducible mouse model is a promising new tool, which might be valuable to test new compounds against AD. Furthermore, this model provides the unique opportunity to study the interplay between Aβ and Tau in AD development and progression.