I think it would be more accurate to state that interactions between APP and presenilin are very likely causative in late onset AD. Currently the known conseque

I think it would be more accurate to state that interactions between APP and presenilin are very likely causative in late onset AD. Currently the known consequence of that interaction is production of Abeta, ergo the amyloid hypothesis. However, if another outcome of that interaction were found, then the "amyloid cascade hypothesis" would be easier to reject. Recent work by several independent groups has focused on disruptions to the endolysosomal system as an alternative causative mechanism, e.g. Lee et al, 2022, discussed in the link below. One should note that despite the claim in the title, the authors may actually finger APP-C99 as causative in the original paper, which I have read very carefully (or rather fail to distinguish between Abeta and APP-C99). https://www.alzforum.org/news/research-news/behold-panthos-toxic-wreath-perinuclear-av-kills-neurons https://www.alzforum.org/news/research-news/behold-panthos-t...