The amyloid-β peptide: Guilty as charged?

Recent years have seen both considerable progress and controversy in the Alzheimer's disease (AD) field. After decades of slow to negligible movement towards the development of disease modifying therapies, promising outcomes in recent clinical trials with several monoclonal antibodies targeting various forms of the amyloid-β (Aβ) peptide have at last opened a possible way forward. In fact, at this point multiple anti-Aβ therapeutics are close to receiving (or have already received) regulatory approval. Although these outcomes are not without some degree of divisiveness, the fact remains that targeting amyloid for removal has finally shown at least modest efficacy in slowing the otherwise relentless progression of the disease. Although the validation of the long standing amyloid cascade hypothesis would seem to be at hand, what remains is the puzzling issue of why - if Aβ indeed causes AD - does removing it from the brain not stop the disease entirely.

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Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.