. Farewell, 'renegade researcher': your voice will be missed. J Neurochem. 2012 Jan;120 Suppl 1:1-2. PubMed.


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  1. With the anticipated implementation of NAPA, it is important to keep in mind the thoughts and observations summarized in this poignant commentary. I also recommend Mark Smith's review (Castellani and Smith, 2011). In my ongoing discussions with those in the AD field, he may not have been as much of a renegade as his wife thinks, but rather, the many AD researchers who agree with his perspective haven't yet coordinated to shift the research playing field.

    The key points are taken from the J Pathol abstract: "With each failure of anti-amyloid-β therapy in clinical trials, new trials are initiated with no hint of slowing down. This may be due, in part, to the fact that the amyloid cascade hypothesis has been so modified over time that it is now impossible to confirm or deny…. The amyloid cascade hypothesis continues to dominate the Alzheimer’s disease literature and grant applications. The more the neuroscience community perseverates along these lines in the face of accumulating outcome data to the contrary, the more one is left to wonder whether the hypothesis is too big to fail."

    Perhaps now is an opportune time to consider this. If you agree, please let your opinions be heard during the upcoming discussions regarding the framework of NAPA.


    . Compounding artefacts with uncertainty, and an amyloid cascade hypothesis that is 'too big to fail'. J Pathol. 2011 Jun;224(2):147-52. PubMed.

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