How Not to Study a Disease

Neurobiologist Karl Herrup explains why Alzheimer's discoveries from the 1990s failed to produce cures and maps a new research direction. The book critiques the field's overemphasis on amyloid, calling out stubbornness, greed, and bad advice that hampered progress, including sharp criticism of FDA-approved drug Aducanumab. Despite the criticism, Herrup offers an optimistic roadmap presenting a fresh conceptualization of aging and dementia that imagines the brain as interconnected "neighborhoods."

8 sections ยท 26 lessons

Course outline

Human Impact

  1. Human Cost
  2. Human Impact

Disease Definition Crisis

  1. Auguste Deter
  2. Politics & Naming
  3. Rare to Common
  4. Preclinical Diagnosis
  5. Disease Definition Crisis

Amyloid Hypothesis Origins

  1. Amyloid Cascade
  2. Genetic Evidence
  3. Amyloid Hypothesis Origins

Hypothesis Failure

  1. Three Failed Tests
  2. Trial Failures
  3. Aduhelm Scandal
  4. Hypothesis Failure

Systemic Problems

  1. Hypothesis to Dogma
  2. Pharma Incentives
  3. Mouse Models
  4. Replication Crisis
  5. Systemic Problems

Alternative Frameworks

  1. Age-Based Hypothesis
  2. Neuroinflammation
  3. Cell Cycle Reentry
  4. Brain Neighborhoods
  5. Alternative Frameworks

Path Forward

  1. Disease Definition
  2. Alternative Directions
  3. Systemic Reforms
  4. Grounds for Optimism
  5. Path Forward

Broader Lessons

  1. Science to Ideology
  2. Strategic Definitions
  3. Translation Failure
  4. Systems Thinking
  5. Broader Lessons

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