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 hypothesizes a link between transgender identity, optical illusions, and NMDA receptor function, based on survey data and existing research on schizophrenia and autism. Longer summary

Scott Alexander explores a potential link between transgender identity, optical illusions, and NMDA receptor function in the brain. He presents survey data suggesting that transgender individuals, like those with schizophrenia and autism, are less susceptible to certain optical illusions. He hypothesizes that this might be related to NMDA receptor hypofunction, which is also associated with dissociation, a common experience among transgender people. The post explores how estrogen, which enhances NMDA function, alleviates dissociation in trans women. Scott connects these findings to broader research on NMDA receptors in schizophrenia and autism, noting the higher prevalence of these conditions in transgender populations. The post concludes with several caveats and suggestions for future research to validate these speculative connections. Shorter summary