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One of the major neuropathological features of Alzheimer’s disease (AD), and other related neurodegenerative disorders, is the presence of abnormal twisted threads of protein known as neurofibrillary tangles (NFTs) in the brain. These are found within neurons in specific regions of brain responsible for learning and memory, as well as other regions as the disease progresses. NFTs are thought to contribute to neurodegeneration, nerve cell death and eventually dementia. The chief component of NFTs is the microtubule binding protein tau. In a healthy brain, tau is associated with microtubules and helps stabilize the neuronal microtubule-skeleton and normal neuronal function. However when tau aggregates and twists into NTFs it is no longer available for binding and stabilizing; as a result the neuronal skeleton falls apart, contributing to neurodegeneration, neuronal cell death and dementia. Using an in vitro, high throughput-screen scientists at Neuronautics Inc, have screened a focused library of more than 3,000 compounds and identified potent several inhibitors of NFT formation. Several of these compounds were shown to effectively inhibit NFT formation in a fish (i.e. lamprey) model. Dr. Hutton in collaboration with scientists at Neuronautics will test the efficacy of the lead compound, NN13, in a transgenic mouse model of NFT formation. Read-outs will include measurements of NFT formation, neurodegeneration and behavior. These studies will pave the path to the development of NN13 and similar compounds and lead to the development of second generation of anti-tangle compounds for Alzheimer’s disease therapy.