Has Fraud Really Hijacked Alzheimer’s Science? Book Review: Charles Piller’s ‘Doctored’

In his book “Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer’s” (Atria, 2025), investigative journalist Charles Piller argues that research fraud and misconduct have significantly impeded progress toward better Alzheimer’s treatments. The book’s controversial claims were in the spotlight during Senate confirmation hearings for Health and Human Services Secretary Robert F. Kennedy Jr., who referenced Piller’s critique to assert that the NIH had failed to pursue meaningful Alzheimer’s research and later used it to defend firing scientists. 

In the pages of “Doctored,” Piller contends that, unlike fields such as heart disease or diabetes — where research breakthroughs have reduced mortality and saved lives — Alzheimer’s research has not delivered comparable advances. He points the finger at unscrupulous scientists chasing after a hypothesis built on on weak or falsified data, effectively crowding out alternative approaches.

His case centers on the amyloid hypothesis: the long-standing idea that toxic accumulations of beta-amyloid proteins (especially soluble oligomers) drive Alzheimer’s pathology. In particular, Piller spotlights the infamous 2006 Nature paper by Sylvain Lesné, which claimed a specific oligomer, Aβ*56, was directly responsible for memory impairment in mice. Subsequent investigations revealed manipulated images in the paper, and it was eventually retracted—yet not before it had been cited thousands of times and heavily influenced subsequent amyloid research.

According to Piller, the reinforcement of such flawed findings set off a cascade of funding and attention toward amyloid-centric studies. He notes that research into amyloid oligomers increased by an estimated $333 million over 15 years, though critics argue this figure misrepresents broader funding trends that also boosted work on immunity, vascular factors, infection, and lifestyle interventions.

While Piller’s expose has swayed public perception — some patients and prospective trial participants have called trial sites worried, asking whether they should withdraw — many neurologists remain unconvinced that the instances of fraud he documents undermine the amyloid hypothesis in its entirety.

Is fraud slowing progress toward effective Alzheimer’s treatments?

Piller sets his sights on the amyloid hypothesis, which proposes that the build-up of toxic forms of beta-amyloid proteins in the brain is the main driver of Alzheimer’s. Piller highlights the now infamous 2006 paper by researcher Sylvain Lesné, claiming that a form of beta-amyloid, Aꞵ*56, was responsible for Alzheimer’s-related cognitive decline in mice. The problem: Lesné’s data was fudged. 

It was more than a decade before the paper was investigated and shown to be fraudulent. In that time, its influence had spread far and wide: It had amassed more than 3,500 citations in other scientists’ research and, Piller suggests, cemented it as a promising and central line of research in Alzheimer’s. 

According to publicly available grants data, Lesné’s paper didn’t have a disproportionate impact. Though research into clumps of beta-amyloid like Aꞵ*56 , also called oligomers, skyrocketed by $333 million within 15 years of the paper’s publication, the numbers Piller cites are cherry-picked and don’t reflect the increase in funding across the board for research into the immune system, blood pressure, infection, and diet as drivers of the disease. 

Some of the grants he includes don’t even focus on developing therapeutics against oligomers; they’re lifestyle intervention studies. In addition, most of the trials for Alzheimer’s disease funded by the NIH are designed to investigate lifestyle or non-drug interventions. Of those that do test drugs, the number of amyloid-focused drug trials has declined in the last decade. In 2013, five out of 14 — or 36 percent — of Alzheimer’s drug trials focused on amyloid. By 2023, there were only eight out of 54 drug trials — or 15 percent — that did so.  

Does all the other amyloid fraud invalidate the hypothesis?

Piller uncovered other instances of suspected amyloid-related fraud. Among them is Eliezer Masliah, chief advisor to the director of the National Institute of Aging, whose prolific record of manipulated research also influenced Parkinson’s drug trials. Cassava Sciences drug simufilam failed in Phase 3 trials amid fraud allegations. A scientist who developed the drug is facing criminal indictments while former executives settled with the SEC for making misleading statements about the drug.  

But, experts say that isn’t enough to overturn the decades of genetic evidence supporting the amyloid hypothesis. Even some of its most vehement critics disagree with Piller on that point.

Karl Herrup, a neurobiologist at the University of Pittsburgh, laid out his own critique in his 2023 book How Not to Study a Disease. However, Herrup disagrees with Piller’s central argument that these cases of fraud have indelibly shaped the field. Herrup also disagreed that Lesné alone was responsible for the theory’s prominence.

“I am confident in saying that if we were able to magically prevent all the fraudulent papers from ever having appeared, the field would not be perceptibly changed,” Herrup wrote of Piller’s book on AlzForum. “The amyloid cascade hypothesis would still dominate the field, and it would still exert ‘enormous pressure towards scientific conformity’.”

Piller told Being Patient, “I think some critics mischaracterized the book as saying that all work on amyloid has been a waste of time.” He emphasized that while there’s no actual organized amyloid cabal, there has been a “concerted effort” to promote the amyloid hypothesis at the “expense of other ways of thinking about the disease.”

It’s a story less of conspiracy and criminality than one of false hope, misapplied science and missed opportunities. “There’s a small percentage of people who cut corners or engage in outright fraud,” Piller told us, adding, “The vast majority of scientists, generally and within Alzheimer’s disease, are honest and people of integrity.”

Amyloid followers and the rise of the “mab”

The book extends the accusations of fraud to question the effectiveness of anti-amyloid monoclonal antibody drugs for Alzheimer’s disease. While there was controversy over the first anti-amyloid drug to hit the market (and the first to be withdrawn), Aduhelm, its successors haven’t faced the same litany of problems. In the clinical trials for Aduhelm’s “mab” drug successors, Leqembi and Kisunla, data shows that targeting beta-amyloid slows cognitive decline — and there have been no accusations nor findings of wrongdoing, fraud, or fudged numbers on these drugs. 

While neurologists may debate whether the minor-to-moderate cognitive benefits of these drugs outweigh the financial cost and risks of side effects (which real-world data has shown is low), the trials have shown small benefits over 18 months. And new trials are testing them in genetically at-risk participants who are not yet symptomatic of Alzheimer’s to understand whether they would be more effective if administered earlier, after amyloid build-up commences but before symptoms set in.

Dr. Nicholas Villain, a neurologist from the Sorbonne, does not discount the troubling discoveries of fraud but thinks Piller is overplaying his hand by connecting them to Leqembi and Kisunla.

“On the one hand, I think he is very correct about the misconduct and saying that the field has not been responsive,” Villain told Being Patient. “On the other hand, I don’t think that it has any impact on the amyloid hypothesis and the drugs that are being developed right now.” 

The ‘Doctored’ effect on research and health policy

Health and Human Services Secretary Robert F. Kennedy Jr. cited the book during his confirmation hearings and recently reiterated the idea that the amyloid hypothesis was based on “utter corruption.” 

While Piller agrees with the idea that institutions need to be reformed to become less complacent with fraud, he told Being Patient that he “tremendously disagrees” with the way the Trump Administration has enacted such reforms and opposes budget cuts and firings in federal research. “I do not think that the historical knowledge and wisdom and the institutional knowledge of these agencies should be stripped out by the firing or forcing out of important scientists who are leading these agencies,” Piller said.

In addition, the book has had an impact on anti-amyloid research trials. Though Leqembi and Kisunla are approved in the U.S. and several other countries, the drugs are difficult for most Americans to access, and uptake has been slow. Doctors and trial administrators say Piller’s book isn’t helping. 

Dr. Resia Sperling, a neurologist at Mass General Research Institute who oversees the AHEAD-3,45 prevention trial, told Being Patient that several people called trial sites after reading book excerpts and reviews in The New York Times and other outlets, asking whether they should drop out of the trial. The trial is a public-private partnership, where researchers receive funding from both the NIH and the drugmaker Eisai to conduct the study. 

Sperling said, “They have contacted the site saying: ‘Well, wait a minute, does this mean I’m in a trial testing amyloid where there’s no evidence supporting that?’” In most of the cases, trial staff and investigators reassured the participants, and they remained in the trial. 

Piller defended his work as shining a needed light and corrective on a suspect area of research that has become all too dominant in the Alzheimer’s field. “I think an intellectually honest person reading these materials would see that I’ve shown reasons why there should be concern about these drugs and their effectiveness and their safety,” he said. 

At the same time, Piller emphasized that he isn’t a doctor, and decisions about whether or not to take any drug ultimately depends on the patient and their healthcare professionals. “It’s completely reasonable for someone to decide to take these drugs,” he said, “given the lack of other remedies for Alzheimer’s disease.”