MAPT and Alzheimer disease: It has been reported that synthetic tau-preformed fibrils and pathological tau derived from brains of AD patient are capable of causing tau aggregation in both cultured cells and wild type mice (155, 156), and that the cell-to-cell spread pattern of the seed-competent tau conformers in the central nervous system (CNS) was determined by synaptic connectivity (e.g., afferent and efferent connections) rather than spatial proximity (156–159).