The Optispan Podcast with Matt Kaeberlein Why 400+ Alzheimer's Drugs Failed (Here's What Works)
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Oct 5, 2025 Dr. Cory, a systems biologist at the Institute for Systems Biology and co-founder of Fulcrum, explores innovative perspectives on Alzheimer's. He argues that it's not just about amyloid plaques, but rather a flawed debris management system in the brain, particularly concerning cholesterol. Discussing the roles of genes like ApoE4 and the impact of lifestyle factors, he sheds light on why current drugs often fail. Dr. Cory also highlights practical prevention tips, emphasizing sleep, diet, and personalized lifestyle choices to combat Alzheimer's.
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Modeling Needs Feedback And Mass Balance
- Modeling brain homeostasis needs multi-scale feedback loops and mass-balance constraints.
- Cholesterol homeostasis is central because membrane cholesterol critically modulates cell signaling.
Test Models Against Population Patterns
- Validate models by reproducing population-level biomarkers like APOE-stratified incidence curves.
- Digital twins work best when they reconcile diverse orthogonal datasets, not perfect precision of one measure.
Amyloid Removal Isn't The Root Fix
- Amyloid removal helps but doesn't stop neuron loss because it doesn't address the root cause.
- Brain shrinkage during antibody therapy suggests upstream drivers remain active.
