Recapitulation of Endogenous 4R Tau Expression and Formation of Insoluble Tau in Directly Reprogrammed Human Neurons

Tau is a microtubule-binding protein expressed in neurons and the equal ratio between 4-repeat (4R) 3-repeat (3R) isoforms are maintained normal adult brain function. Dysregulation of 3R;4R causes tauopathy human that recapitulate tau health disease will provide platform for elucidating pathogenic processes involving pathology. We carried out extensive characterizations derived by microRNA-induced neuronal reprogramming fibroblasts. Transcript analyses showed miR-neurons all six with 3R:4R isoform equivalent to detected brains. Also, from familial patients altering mutation increased 4R formation insoluble seeding activity. Our results collectively demonstrate utility miRNA-induced endogenous regulation comparable disease.