Abstract

We have developed a mouse-human chimeric mouse model for Alzheimer’s disease. The human neurons but not the mouse neurons develop the complete spectrum of Alzheimer’s disease pathology from amyloid plaques, up to Tau pathology and to necroptosis of neurons. This full phenotype is seen only in the human neurons not in the mouse neurons of the same chimeric brain. We have used this model to perform an in vivo screen for all human kinases to see which ones are modifying this cascade. To this end we have used a CAS9 inducible system in the transplanted neurons and screened with a lentiviral vector library of suitable guide RNA’s. This work is ongoing but I will share our first results.