An authority on Alzheimer's disease offers a history of past failures and a roadmap that points us in a new direction in our journey to a cure.
For decades, some of our best and brightest medical scientists have dedicated themselves to finding a cure for Alzheimer's disease. What happened? Where is the cure? The biggest breakthroughs occurred twenty-five years ago, with little progress since. In How Not to Study a Disease, neurobiologist Karl Herrup explains why the Alzheimer's discoveries of the 1990s didn't bear fruit and maps a direction for future research. Herrup describes the research, explains what's taking so long, and offers an approach for resetting future research.
Herrup offers a unique insider's perspective, describing the red flags that science ignored in the rush to find a cure. He is unsparing in calling out the stubbornness, greed, and bad advice that has hamstrung the field, but his final message is a largely optimistic one. Herrup presents a new and sweeping vision of the field that includes a redefinition of the disease and a fresh conceptualization of aging and dementia that asks us to imagine the brain as a series of interconnected "neighborhoods." He calls for changes in virtually every aspect of the Alzheimer's disease research effort, from the drug development process, to the mechanisms of support for basic research, to the often-overlooked role of the scientific media, and more. With How Not to Study a Disease, Herrup provides a roadmap that points us in a new direction in our journey to a cure for Alzheimer's.
Author(s): Karl Herrup
Publisher: The MIT Press
Year: 2021
Language: English
Pages: 272
City: Cambridge
Contents
Prologue
I. In The Beginning
1. A Layperson’s History of Alzheimer’s Disease
Dorothy’s Story
Defining Dementia and Alzheimer’s Disease
Alzheimer’s Disease in Our World
The Economic Impact of Dementia
Who Gets Alzheimer’s Disease, and Can the “Who” Tell Us about the “Why”?
Synopsis
2. A Physician’s History of Alzheimer’s Disease
3. A Scientist’s History of Alzheimer’s Disease
Early- versus Late-Onset Alzheimer’s Disease
The Genetics of Sporadic Alzheimer’s Disease
Inflammation of the Brain as a Cause of Alzheimer’s Disease
Poor Fat Management as a Cause of Alzheimer’s Disease
Improper Vesicle Management as a Cause of Alzheimer’s Disease
Nongenetic Clues to the Cause of Alzheimer’s Disease
Back to Plaques and Tangles
4. Mystery Solved! How Four Discoveries Transformed an Entire Field
Unmasking the Plaques
A Short Interlude—Some Basic Genetics
Running the Central Dogma of Molecular Biology Backward
Prying the Amyloid Peptide out of Its APP Parent
We’ve Cured the Mice! we are Almost There
II. What Happened To Our Cure?
5. Building A Model of Alzheimer’s Disease
The Amyloid Cascade Hypothesis Grows . . . into a Bully
Other Options: Inflammation of the Brain as a Cause of Alzheimer’s Disease
Other Options: Poor Fat Management as a Cause of Alzheimer’s Disease
Other Options: Loss of Myelin Integrity as a Cause of Alzheimer’s Disease
Interlude: An Optional Deep Dive into the Realities of Human Scientific Data
Back to Myelin
Other Options: Improper Vesicle Management as a Cause of Alzheimer’s Disease
Other Options: Oxidative Damage and Mitochondrial Dysfunction as a Cause of Alzheimer’s Disease
Other Options: Tau as a Cause of Alzheimer’s Disease
Synopsis
III. Double-Edged Swords
6. Federal Support of Basic Biomedical Research
7. The Pharmaceutical and Biotech Industry
History of the Pharmaceutical Industry
Why Do We Need Them?
The Industrial Approach to Research and Development
Outsourcing
They Saw the Warning Signs, and yet They Did Nothing
8. Testing Our Models: Breaking Bad
Testing the Hypothesis I: Add Amyloid, Create Alzheimer’s Disease
Experimental Models of Human Disease
Testing the Hypothesis II: Remove Amyloid, Cure Alzheimer’s Disease
Testing the Hypothesis III: Block Amyloid from Ever Forming
Grading the Tests: The Amyloid Cascade Hypothesis Flunks the Course
Houston, We Have a Problem
9. What Is Alzheimer’s Disease?
Doubling Down
The Third Inflation
The Final Straw
IV. Where Shall We Go From Here?
10. A Layperson’S Guide to the Biology of Aging
Why Do we Age?
What Drives Our Aging Process?
Age and the Single Cell
Summary
11. Building A New Model of Alzheimer’s Disease
The Definition of Alzheimer’s Disease—The Foundation of All Future Work
A Biological Model of Alzheimer’s Disease
12. Rebalancing Our Research Portfolio
The Biology of Aging
The Aging of the Neighborhood
The Biology of Alzheimer’s Disease as Seen through the New Model
The Search for Biomarkers
The Aging of the Nation and Its Contribution to Alzheimer’s Disease
Critiquing the Model
13. Rebalancing Our Institutions
The Definition of Alzheimer’s Disease and the Cabal
Adjusting Government Funding of Alzheimer’s Disease Research
Adjusting the Role of the Pharmaceutical Industry
Adjusting the Role of the Advisors
Adjusting the Roles of Our Professional Societies
Adjusting the Role of the Professional and Lay Media
Synopsis
14. Final Thoughts
Acknowledgments
Notes
Chapter 1
Chapter 2
Chapter 3
Chapter 4
Chapter 5
Chapter 6
Chapter 7
Chapter 8
Chapter 9
Chapter 10
Chapter 11
Chapter 12
Chapter 13
Index
