A philosophy of science approach to the amyloid hypothesis of Alzheimer's disease.

Abstract

Disputes about the scientific validity of the amyloid-β hypothesis of Alzheimer's disease have been held since the early 1990s, with little constructive progress made between opposing sides despite recent therapeutic progress. Here, I argue that philosophy of science can improve the chance of constructive debate by giving researchers technical language to describe and assess scientific progress. To do so, I interpret the amyloid hypothesis using a modified version of the research programme concept from philosopher of science Imre Lakatos. I first outline the amyloid-β hypothesis and study critiques of its central place in Alzheimer's research. Then, I draw on the complexity of amyloid-β and Alzheimer's research to discuss the limits of using concepts from popular philosophers of science Karl Popper or Thomas Kuhn, before finally arguing that an adaptation of the research programme concept can foster constructive debates about the science of Alzheimer's and within it. I will argue that the amyloid-β hypothesis has contributed to significant progress in the Alzheimer's field based on what Lakatos called the "positive heuristic" (motivating the programme to test its predictions) and the "negative heuristic" (protecting the programme from refutation). I consider the amyloid research agenda to be progressive despite the fact that its claims about disease aetiology could be wrong.