MAPT and Alzheimer disease: This CVN-AD model (APPSwDI +/+/mNos2-/-) of AD replicates extensively the histological and behavioral characteristics of the human disease including early onset of amyloid plaques by 12 weeks, phosphorylated tau by 24-36 weeks, and significant cell loss and behavioral changes by 36 weeks, replicating most human changes in pre-clinical and clinical aspects of AD (Fig. 3 shows the time course).