The DeArmond Neuropathology Research Laboratory has focused on the cell biological and molecular mechanisms of neurodegeneration in prion diseases. His accomplishments include showing that amyloid plaques in Creutzfeldt-Jakob disease are composed of PrP^Sc and that accumulation of non-amyloid PrP^Sc in the brain is the cause of early synaptic dysfunction and degeneration and the cause of late occurring nerve cell death. More recently, he has been testing whether PrP^Sc accumulation alters expression of genes known to play critical roles in presynaptic and postsynaptic growth and maturation during CNS development. He found a direct correlation between synaptic PrP^Sc accumulation and activation of Notch-1 releasing the Notch-1 intracellular domain (NICD). NICD is a transcription factor that ultimately decreases expression of genes that maintain dendritic and axonal lengths. This finding argues that synapse degeneration in prion diseases is a programmed event (synoptosis) similar to programmed nerve cell death (apoptosis). A clinical implication of this finding is the potential that prevention of Notch-1 activation by pharmaceutical agents might prevent progressive cognitive decline in prion diseases and possibly even in other dementing disorders.