A guest post defending the amyloid hypothesis of Alzheimer's disease, explaining why amyloid is likely the root cause despite recent criticism and discussing why early treatments have only been partially effective. Longer summary

David Schneider-Joseph presents a detailed defense of the amyloid hypothesis of Alzheimer's disease, which states that the disease is caused by accumulation of amyloid-β peptide. He explains the ATN model (amyloid → tau → neurodegeneration) and provides extensive evidence from genetics, clinical studies, and animal models. The post addresses various criticisms of the hypothesis, including the recent research fraud controversy and apparent failures of early treatments. The author explains why current treatments have only achieved about 30% efficacy and predicts that future treatments targeting amyloid earlier and more effectively could achieve much better results. Shorter summary

A detailed review of a 1995 paper introducing the PDAPP mouse model for Alzheimer's disease, examining how its limitations were overlooked and shaped decades of potentially misguided Alzheimer's research. Longer summary

The post reviews a landmark 1995 paper introducing the PDAPP mouse model for Alzheimer's disease, analyzing how its technical achievements and limitations shaped three decades of Alzheimer's research. The author examines the paper's methodology, results, and claims, showing how the model's flaws - including extreme protein overexpression and lack of key disease features - were overlooked in favor of a compelling but incomplete amyloid cascade hypothesis, leading to years of failed drug development and missed opportunities to explore alternative approaches. Shorter summary

Scott Alexander critiques a study suggesting knowledge of ApoE4 gene status affects memory performance, arguing the results may be due to priming or stereotype threat rather than actual memory decline. Longer summary

Scott Alexander discusses a study by Lineweaver et al. that tested elderly adults for the ApoE4 gene, a risk factor for Alzheimer's. The study found that subjects who knew they had ApoE4 performed worse on memory tests than those who had it but didn't know. Scott critiques the study's methodology and interpretation, suggesting that the results might be due to priming effects or stereotype threat rather than actual memory decline. He expresses concern that the medical community might overinterpret these results and discourage genetic testing without sufficient evidence of harm. Shorter summary