Neurofibrillary tangles (NFTs), a marker of neuronal alterations in Alzheimer's 
disease (AD) and other tauopathies, are comprised of aggregates of 
hyperphosphorylated tau protein. We recently studied the formation of NFTs in 
the entorhinal cortex (EC) and their subsequent propagation through neural 
circuits in the rTgTauEC mouse model (de Calignon et al., 2012). We now examine 
the consequences of suppressing transgene expression with doxycycline on the 
NFT-associated pathological features of neuronal system deafferentation, NFT 
progression and propagation, and neuronal loss. At 21 months of age we observe 
that EC axonal lesions are associated with an abnormal sprouting response of 
acetylcholinesterase (AChE)-positive fibers, a phenotype reminiscent of human 
AD. At 24 months, NFTs progress, tau inclusions propagate to the dentate gyrus, 
and neuronal loss is evident. Suppression of the transgene expression from 18 to 
24 months led to reversal of AChE sprouting, resolution of Gallyas-positive and 
Alz50-positive NFTs, and abrogation of progressive neuronal loss. These data 
suggest that propagation of NFTs, as well as some of the neural system 
consequences of NFTs, can be reversed in an animal model of NFT-associated 
toxicity, providing proof in principle that these lesions can be halted, even in 
established disease.