Heresy, Orthodoxy & Time
Following up on yesterday's discussions about lecanemab , some points to address. Maybe I am old-fashioned, but I believe that science should be about well-defined entities and mechanisms. I also believe that scientific theories should not be self-contradictory and must make sense within the known laws of physics, chemistry, and biology. From this perspective, I do not think that the two major hypotheses used to describe the amyloid phenomenon (The Amyloid Cascade Hypothesis (ACH) & The Prion Hypothesis (PrH)) fulfill these criteria. I also think that this is the reason behind much of the confusion and the scarcity of clinical success in the field. The ACH & the PrH were unorthodox hypotheses when they were developed in the 80s & 90s. The ACH boldly stated, in contrast to conventional biological and physicochemical wisdom at the time, that the endogenous proteins that form aggregates, even if evolutionary conserved & highly expressed in their native state, are j...