Organotypic slice cultures have been prepared from the brains of transgenic mice with Alzheimer's disease-type pathology. Cell types within the slice undergo differentiation and slices can be maintained in culture for up to 6 mo when prepared from young neonates. Slices have been prepared from mice overexpressing genes of relevance to Alzheimer's disease, including mutant or wild-type tau. Neurons in these slices develop neurons that are immunoreactive for a number of markers of abnormal tau. Organotypic slice models are currently being used to test the impact of tangle enhancers or inhibitors as a prescreen for efficacy before testing drugs in vivo.