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. APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature. 2009 Feb 19;457(7232):981-9. PubMed.

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  1. This paper provides extensive and compelling evidence for β-APPs (shed from the cell surface by β-secretase) being a major agonist for the cell death receptor DR6, a key signaling pathway in the neuronal pruning that takes place during development. Finally, a clear study on the normal biological function of APP: a seminal paper, in my view. However, too much is made of possible implications to AD. For instance, this mechanism does not explain any of the FAD mutations in either APP, PS1, or PS2 (except perhaps adding an additional mechanism for the pathogenesis of the APP Swedish mutation near the β-secretase cleavage site).