Alzscammers

Charles Piller, an Oakland-based investigative reporter for Science magazine, is soft-spoken in person and in print. In his new book, “Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer’s,” dynamite accusations are professionally gift-wrapped. ”In some cases, the data problems might have an innocent explanation,” Piller wrote in a NY Times essay previewing the book. “Some researchers who put their names on papers may not have been aware of errors made by co-authors, but other cases most likely involve serious negligence, misconduct and outright fraud.”

Piller's “most likely” is a polite way of saying “obviously.”

“Take for example the revered neuroscientist Eliezer Masliah, whose groundbreaking research has shaped the development of treatments for memory loss and Parkinson’s disease, and who in 2016 was entrusted to lead the National Institute on Aging’s expanded effort to tackle Alzheimer’s. With roughly 800 papers to his name, many of them considered highly influential, Dr. Masliah seemed a natural choice to steer the project, with billions in new funding. He hailed the moment as the dawning of 'the golden era of Alzheimer’s disease research.'

“Last September in Science magazine, I described evidence that for decades Dr. Masliah’s research had included improperly manipulated photos of brain tissue and other technical images — a clear sign of fraud. Many of his studies contained apparently falsified western blots — scientific images that show the presence of proteins in a blood or tissue sample. Some of the same images seem to have been used repeatedly, falsely represented as original, in different papers throughout the years. (When I reached out to Dr. Masliah for the story, he declined to respond.)

The day Piller's piece appeared in Science, Masliah lost his position.

“I then asked a team of brain and scientific imaging experts to help me analyze suspicious studies by 46 leading Alzheimer’s researchers… Collectively, the experts identified nearly 600 dubious papers from the group that have distorted the field — papers having been cited some 80,000 times in the scientific literature. Many of the most respected Alzheimer’s scholars — whose work steers the scientific discourse — repeatedly referred to those tainted studies to support their own ideas. This has compromised the field’s established base of knowledge.”

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The disease afflicts nearly seven million Americans, about one in every nine people over the age of 65, making it a leading cause of death among older adults. Up to 420,000 adults in the prime of life — including people as young as 30 — suffer from early-onset Alzheimer’s. The annual number of new cases of dementia is expected to double by 2050…

In the United States, more than 11 million family members and other unpaid caregivers (such as friends and neighbors) care for fathers and mothers, spouses and grandparents who have fallen prey to dementia. For many this means financial impoverishment. These caregivers in the United States provided the equivalent of nearly $350 billion in care to dementia patients in 2023 — nearly matching the amount paid for dementia care by all other sources, including Medicare.

Despite decades of research, no treatment has been created that arrests Alzheimer’s cognitive deterioration, let alone reverses it.

For decades, Alzheimer’s research has been shaped by the dominance of a single theory, the amyloid hypothesis. It holds that amyloid proteins prompt a cascade of biochemical changes in the brain that cause dementia… Many of the most hardened skeptics of the hypothesis believe that amyloids have some association with the disease. But since the early 2000s, doctors, patients and their loved ones have endured decades of therapeutic failures stemming from it, despite billions of dollars spent in grants and investments. Its contradictions — such as the presence of massive amyloid deposits found in the brains of deceased people who had no symptoms of Alzheimer’s — have long exasperated critics and prompted doubts among many supporters.

Still, the hypothesis retains enormous influence. Nearly every drug approved for Alzheimer’s dementia symptoms is based on it, despite producing meager results. The anti-amyloid antibody drugs approved in the United States cost tens of thousands of dollars per patient per year, yet they slow cognitive decline so minutely that many doctors call the benefits imperceptible. The drugs are also not benign, posing risks of death or serious brain injury, and they can shrink the brain faster than Alzheimer’s itself.

The entrenchment of the amyloid hypothesis has fostered a kind of groupthink where grants, corporate riches, career advancement and professional reputations often depend on a central idea largely accepted by institutional authorities on faith. It’s unsurprising, then, that most of the fraudulent or questionable papers uncovered during my reporting have involved aspects of the amyloid hypothesis. It’s easier to publish dubious science that aligns with conventional wisdom…

Questionable and potentially fraudulent studies by Dr. Masliah and that of many others, have helped lay the foundation for hundreds of patents related to Alzheimer’s and Parkinson’s treatments and techniques, now being pursued by leading pharmaceutical companies.

For example, Hoau-Yan Wang, whose work contributed to the development of simufilam — an Alzheimer’s drug tested on thousands of patients — has faced credible allegations of image doctoring and manipulated test results. Dr. Wang was indicted by the Department of Justice in June 2024 on charges that he defrauded the National Institutes of Health of $16 million in grants. He has pleaded not guilty. The biopharmaceutical company backing the drug, Cassava Sciences, settled with the U.S. Securities and Exchange Commission on charges that the company and key executives had misled investors on research around the drug. The executives did not admit wrongdoing… (They made millions in salary and stock trades despite simufilam crashing and burning.)

Recently, alternatives to the amyloid hypothesis have begun to find support. Promising approaches include exploring the role of viruses in cognitive decline, treating brain infections and reducing brain inflammation — potentially with GLP-1 drugs that have transformed weight loss. There’s also growing evidence that healthy lifestyle choices, as well as controlling blood pressure and cholesterol, can slow the disease’s progression.”

… The broader incentive structures in science — where pressure to publish, secure funding and achieve breakthroughs is immense — can lead even well-meaning scientists to make shocking choices.

A slippery slope sometimes begins when a researcher alters highly enlarged pictures of brain slices to enhance them aesthetically — seemingly “harmless” doctoring to clarify biology’s inherent messiness and ambiguity. Beautiful images increase a paper’s curb appeal for publishers. (That temptation has been especially enticing amid a publish-or-perish imperative for scientists that’s so extreme it has spawned an industry of pay-to-play paper mills. Shady companies churn out phony scholarly papers, then sell author slots to desperate or ethically challenged academics.)

Scientists may then find themselves changing an image to strengthen its frail support for an experimental premise. They might rationalize their behavior as simply polishing a potentially important outcome. Scholarly journals have overlooked or been fooled by such deceits over and over. Scientists who are devoted to their assumptions regardless of the evidence — or outright cynics — may then take that deceit a step further. They fundamentally change images to fit their hypotheses: unambiguous misconduct.

Decades of complacency by funders, journals and academic institutions that manage the research enterprise means that relatively few cases of such fraud have been caught. For example, few peer reviewers who certify a paper’s scientific quality have the skill to check for image tampering. Despite years of scandals, many journal editors don’t verify images either. And few perpetrators face meaningful consequences.

So with professional rewards potentially great, many scientists, including those of high standing, seem to roll the dice. They surely know that misconduct investigations are nearly always conducted by an accused researcher’s home university, which fears the loss of face and funding that might follow a prompt, robust and open process. Such investigations — often lasting many months or years — usually start and finish behind a bureaucratic veil, hidden from public view.

A Key Source

Great reporting usually involves great sources. On the Association for Healthcare Journalists' website, Piller wrote in 2022:

“A tip connected me last December with a whistleblower — neuroscientist and physician Matthew Schrag — who had doubts about the research behind Simufilam — an investigational drug from Cassava Sciences. He found more than 170 seemingly doctored images and other possible data manipulations in studies related to the drug or other papers by Cassava-affiliated scientists.

“Schrag had also started to explore the work of University of Minnesota researchers Sylvain Lesné and Karen Ashe, who in 2006 discovered Aβ*56 (“amyloid beta star 56”) — a toxic, soluble protein. Ashe described it as the first causal link between a particular substance and Alzheimer’s symptoms. Their breakthrough supported the amyloid hypothesis — the dominant idea that certain amyloid proteins form the sticky deposits and other toxic molecules that kill nerve cells and lead to devastating cognitive impairment. The Lesné-Ashe findings boosted faith in that hypothesis when it faced increasing skepticism and needed experimental validation.

“Their seminal 2006 paper in Nature on AB-56 has been cited in the scientific literature about 2,300 times — the fourth most for any of the thousands of basic-research papers about Alzheimer’s since it was published.

“I contacted Schrag just as he began to grasp that his findings could have far-reaching influence. If he was right, years of research and billions of dollars in research and development funding had been influenced by work with unreliable or false conclusions. Schrag found that Lesné appeared to have doctored key images in the Nature study and nine other papers supporting AB-56.”

Piller, a professional science writer at the top of his game, thanks his primary source: “By calling out powerful agencies, journals, and scientists, Schrag might jeopardize grants and publications essential to his success. But he says he felt an urgent need to go public about work that might mislead the field and slow the race to save lives. ‘You can cheat to get a paper. You can cheat to get a degree. You can cheat to get a grant. You can’t cheat to cure a disease,’ he says. ‘Biology doesn’t care’.”