Show 1416: Exposing Fraud and Arrogance in Alzheimer's Research

This week, we explore the evidence that some respected researchers in the field of Alzheimer’s disease took shortcut or even manipulated their data to get the results they wanted. How did our guests detect fraud and arrogance in this research?

Exposing Fraud & Arrogance in Alzheimer’s Research:

With nearly seven million Americans currently suffering from Alzheimer’s disease, the effort to understand what causes it and how it could be treated effectively is urgent. Over the last several decades, research on this dementia has focused largely on amyloid plaque (also called amyloid-beta) in the brain as the sole cause. Consequently, drug companies have developed medications that can pull plaque out of the brain. Medicines like aducanumab (Aduhelm), lecanemab (Leqembi) and donanemab (Kisunla) do that pretty well. Unfortunately, though, the patients don’t get better. At best, they decline a little more slowly. Could putting all the focus on amyloid-beta have been a mistake?

Western-Blot Images Appear to Have Been Changed:

Dr. Matthew Schrag is a neurologist who has been examining images in scientific papers independently of his university duties at Vanderbilt. His initial investigations were of studies of a drug called simufilam being developed by Cassava Sciences. He detected signs suggesting that some of the images (termed “Western blot”) indicating proteins present in certain tissues had been altered. To interpret such images appropriately, a person needs a high level of expertise. Changing the picture can change the interpretation of the data as well.

The Risks of Blowing the Whistle:

An investigative journalist for Science magazine, Charles Piller, heard about Dr. Schrag’s discoveries and wrote an in-depth story about it. Dr. Schrag had not set out to be a whistleblower. Both he and Mr. Piller were well aware of the hazards whistleblowers can run, especially if they are early in their careers. However, they are both curious people and dedicated to research integrity. Dr. Schrag had found some disturbing signs in foundational papers of the field. Charles Piller thinks of him as the most important whistleblower in the history of Alzheimer disease research.

The two men teamed up to take a closer look. What could account for the apparent image manipulation that they uncovered? As Mr. Piller observes, the incentives for scientists encourage data manipulation if one is so inclined. Getting journals to retract published papers is difficult. Universities are likewise not eager to investigate prominent investigators. Mr. Piller and Dr. Schrag are careful not to imply that the field is rife with fraud and arrogance. However, they found far more than we should be comfortable with.

Verification:

Mr. Piller invited other experts to review the images that Dr. Schrag had flagged as questionable. In most cases, they agreed that someone had apparently tinkered with them. In some cases, images reappeared in multiple papers. Since they are an important form of data, they should not be replicated in papers describing different experiments.

The Problems with Amyloid Drugs:

It seems very odd that the FDA approved aducanumab (Aduhelm) despite the recommendation of its expert panel not to do so. Aduhelm has since been removed from the market. Like other drugs in the class, it has a small benefit–almost imperceptible from the perspective of the patients or their families. The side effects could be consequential, however. In some cases, the drug causes swelling or bleeding of the brain. It also can result in ARIA, amyloid-related imaging abnormalities. Over time, these medications end up shrinking people's brains even more than the disease itself does.

The Future of Research on Alzheimer’s Disease:

Once fraud and arrogance have been exposed, suspicious findings could be excised from the scientific literature. This should permit research to flourish on a range of approaches to understanding Alzheimer’s disease.

This Week's Guests:

Matthew Schrag MD, PhD, is Assistant Professor of Neurology at Vanderbilt University School of Medicine and Director of the Cerebral Amyloid Angiopathy Clinic. The Schrag Lab is focused on discovering shared molecular pathways between Alzheimer disease and cerebral amyloid angiopathy. His website is https://medschool.vanderbilt.edu/brain-institute/person/matthew-schrag-m-d-ph-d/

[caption id="attachment_123655" align="alignnone" width="768"] Matthew Schrag, MD, PhD, Vanderbilt University[/caption]

Charles Piller is a prominent investigative journalist, primarily known for his work in the field of science. He writes in-depth stories for Science magazine, where he often exposes misconduct and problematic practices within scientific research, particularly focusing on public health issues like the study of Alzheimer's disease. Charles Piller is the author of Gene Wars and The Fail-Safe Society. His most recent book is Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer's.

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You can read an essay by Charles Piller recently published in The New York Times: “The Devastating Legacy of Lies in Alzheimer’s Science.” The photo of Charles Piller is by Mike McGee.

[caption id="attachment_133939" align="alignnone" width="768"] Charles PIller, author of Doctored: Fraud, Arrogance and Tragedy in the Quest to Cure Alzheimer's[/caption]