A review of the synaptic plasticity and memory hypothesis arguing that it is insufficient to explain memory, and proposing a broader cellular processes and memory hypothesis that includes molecular and intracellular mechanisms. Longer summary

The post reviews the synaptic plasticity and memory (SPM) hypothesis, which claims that learning and memory are stored in changes to synaptic weights between neurons. Through several compelling examples, from cannibalism rituals to heart transplant stories and single-cell learning, the author argues that while the SPM hypothesis has been productive, it is incomplete and partially wrong. The post presents evidence that memory can be stored through non-synaptic mechanisms, and proposes an alternative called the cellular processes and memory (CPM) hypothesis, which suggests memory storage involves multiple molecular and intracellular processes beyond just synaptic weights. 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