Quoting his article:
I would bet on the following: A therapy whose sole intended mechanism involves amyloid production or clearance, in a randomized, double-blind, placebo-controlled trial, will, in the next 12 years, achieve a slowdown of cognitive decline of at least 75%, with a p-value below 0.001, in its preregistered primary cognitive endpoint (or an average of all such endpoints if more than one exists). I’d eventually expect better than 75% efficacy, but getting stuff to work takes time, and I wanted to make a prediction which can be tested in a reasonable timeframe.
On the other hand, if a clinical trial completes earlier than 12 years from now (perhaps [73], reading out in 2027), sustains extremely good amyloid clearance at the preclinical stage, and has a good safety profile, but doesn’t make substantial progress towards this 75% goal, then I would consider this prediction refuted in advance.
Resolves yes if the first condition occurs by the end of the market
https://www.astralcodexten.com/p/in-defense-of-the-amyloid-hypothesis
Update 2025-08-18 (PST) (AI summary of creator comment): - No early resolution: The creator intends to wait until the end of the 12-year window (market close) to resolve.
"Refuted in advance" clause: Will not be used for early NO; interim successes also won't trigger early YES.
Stanford paper just published: Aggregation shifts amyloid-β peptides from synaptogenic to synaptotoxic
"Whether amyloid-β (Aβ) peptides are synaptogenic or synaptotoxic remains a pivotal open question in Alzheimer’s disease research. [...] our experiments reveal that Aβ peptides exhibit an aggregation-dependent functional dichotomy that renders them either synaptogenic or synaptotoxic, thereby providing insight into how Aβ peptides straddle a thin line between physiological synapse organization and pathological synapse disruption. Among others, our data suggest that Alzheimer’s disease therapies might aim to shift the balance of Aβ peptides from the aggregated to the free state instead of suppressing all Aβ peptides."
Not related to the market but to the topic: https://aacrjournals.org/cancerres/article-abstract/85/19/3791/765868/Alzheimer-s-Disease-Associated-Amyloid-Precursor?redirectedFrom=fulltext
News article: https://newatlas.com/disease/amyloid-beta-protein-t-cells-mitophagy-cancer/
“What we found is that the same amyloid peptide that is harmful for neurons in Alzheimer’s is actually beneficial for T cells in the immune system,” said Besim Ogretmen, PhD, associate director of Basic Science at Hollings, and the study’s corresponding author. “It rejuvenates the T cells, making them more protective against tumors.”
@Ernie i was just copying from the article without formulating it for a market - i think i will just wait until the end?
@strutheo Thanks for the clarification, that's a massive difference indeed. It might be better to remove the second paragraph from the description to avoid any confusion.