Medical advances have beaten back many relentless assassins in recent decades, such as cancer and heart disease. A wide range of treatments share credit: surgery, medicines, radiation, genetic therapies and healthful habits. Mortality rates for those two diseases, the top causes of death in the United States, have fallen sharply. But in an aging population, Alzheimer’s death rates have gone in the opposite direction.
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.
Yet despite decades of research, no treatment has been created that arrests Alzheimer’s cognitive deterioration, let alone reverses it. That dismal lack of progress is partly because of the infinite complexity of the human brain, which has posed insurmountable challenges so far. Scientists, funders and drug companies have struggled to justify billions in costs and careers pursuing dead-end paths. But there’s another, sinister, factor at play.
Over the past 25 years, Alzheimer’s research has suffered a litany of ostensible fraud and other misconduct by world-famous researchers and obscure scientists alike, all trying to ascend in a brutally competitive field. During years of investigative reporting, I’ve uncovered many such cases, including several detailed for the first time in my forthcoming book.
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.)
It’s true that some image abnormalities can be errors introduced by the publication process. Others might contain innocuous visual artifacts or human errors that sometimes appear to be image doctoring. But in some cases, the volume and nature of the evidence (and the failure of authors to provide raw, original data and images to clear up any confusion) have convinced outside experts that something more troubling has occurred. On the day my story was published, the National Institutes of Health announced that it had found that Dr. Masliah engaged in research misconduct and that he no longer held his leadership position at the National Institute on Aging.
Dr. Masliah epitomized a deeper malaise within the field — a crisis that goes far beyond him. Many Alzheimer’s researchers, including some once considered luminaries, have recently faced credible allegations of fraud or misconduct. These deceptions have warped the trajectory of Alzheimer’s research and drug development, prompting critical concerns about how bad actors, groupthink and perverse research incentives have undermined the pursuit of treatments and cures. It haunts me that this may have jeopardized the well-being of patients.
In my reporting, I asked a team of brain and scientific imaging experts to help me analyze suspicious studies by 46 leading Alzheimer’s researchers. Our project did not attempt a comprehensive look at all 46, let alone the multitude of other Alzheimer’s specialists who contributed to those projects. That would take an army of sleuths and years of work. But our effort was, to my knowledge, the first attempt to systematically assess the extent of image doctoring across a broad range of key scientists researching any disease.
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.
In some cases, the data problems might have an innocent explanation. 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.
Such wrongdoing in any health-related research is lamentable. But fraud in the pursuit of treatments for Alzheimer’s is especially tragic because it’s a disease apart, different in kind from other major killers of the aging. It generally begins by gradually degrading a person’s command of routine activities, then stealing cherished memories and finally the very identity that makes each of us human.
Alzheimer’s families face incalculable emotional costs. 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. The world desperately needs a cure, which makes any misconduct all the more insidious. And it raises an urgent question: Why would a scientist do it?
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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. The supremacy of that hypothesis has exerted enormous pressure toward scientific conformity.
Even 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.
I learned about Dr. Masliah’s apparent deception while reviewing suspicious research papers flagged on PubPeer, a website where scholars and sleuths challenge scientific papers. A few posts about his work caught my eye. I asked the neuroscientist Matthew Schrag of Vanderbilt University, the neurobiologist Mu Yang of Columbia University, the independent forensic-image analyst Kevin Patrick and the microbiologist and research-integrity expert Elisabeth Bik to examine his work closely. (Dr. Schrag and Dr. Yang worked independently from their university jobs.)
Over several months the group created a 300-page dossier comprising 132 papers by Dr. Masliah that they deemed suspicious. (Although the papers were written with colleagues, Dr. Masliah was the sole common author and usually played a leading role.) The experiments in those papers had been cited more than 18,000 times in academic and medical journals. The scale of apparent misconduct, including in many papers related to the amyloid hypothesis, uncovered in just a fraction of Dr. Masliah’s work stunned leading experts.
Although an extreme example, Dr. Masliah fits a pattern of researchers whose work has been called into question.
There’s Berislav Zlokovic, a renowned Alzheimer’s expert at the University of Southern California, whose research informed the basis of a major federally funded stroke trial. My 2023 investigation for Science, aided by the same image sleuths, revealed decades of apparent image manipulation in his studies. The N.I.H. quickly suspended the stroke trial. An attorney representing Dr. Zlokovic claimed that some of the concerns raised about his studies were “based on information or premises Professor Zlokovic knows to be completely incorrect” or were related to experiments not conducted in his lab.
Marc Tessier-Lavigne, the former president of Stanford University, was known as a global leader in research on the brain’s circuitry in Alzheimer’s and other neurological conditions. He resigned in 2023 after an intrepid student journalist revealed numerous altered images in his research. Dr. Tessier-Lavigne didn’t personally falsify data or coerce junior colleagues to do so. But he failed to correct dubious results that came to his attention and may have provided inadequate oversight of his lab — allowing apparently doctored studies that helped build his reputation to remain on the scientific record, according to an investigation by a special committee appointed by the university’s board of trustees. In his resignation letter, Dr. Tessier-Lavigne denied that he had engaged in any unethical research but admitted that there were instances in which he “should have been more diligent in seeking corrections.”
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.
When extensive and credible doubts cast a pall over a scientific portfolio, it’s natural to question the integrity of the researcher’s entire body of work. But not all the research I examined from those scholars was touched by apparent misconduct; some of them have even made contributions that could advance neuroscience, which makes this all the more complicated.
Most Alzheimer’s scholars operate with determination and integrity, and there are many independent-minded scientists advancing our understanding of the brain and memory loss. 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.
But widespread misconduct wastes time, steals precious resources and skews thinking by honest scientists. Meanwhile, the staggering scale of Alzheimer’s grows year by year.
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The question of why any scientist would resort to cheating looms large. Alzheimer’s disease remains one of the most formidable challenges in medicine, and the persistent lack of progress can feel like a deeply personal failure. Such frustration seemingly can, at times, drive normally ethical people to publish provocative results based on doctored data. The lure of prestige, fame and potential fortune from developing desperately needed drugs — even those with little or no realistic hope of benefit — has apparently led astray many who entered the field as seekers of truth. After all, top Cassava Sciences executives made millions in salary and stock trades despite simufilam crashing and burning, as had been long predicted by many experts.
“As a field, we’ve had a lot of dead ends” that have left patients waiting endlessly for treatments, said Donna Wilcock, an Indiana University neuroscientist who edits the journal Alzheimer’s & Dementia. “Some people have put their ego and fame ahead of performing rigorous science.”
That phenomenon is not isolated to Alzheimer’s research. 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.
Dr. Schrag of Vanderbilt, one of the neuroscientists I’ve worked with to uncover cases of scientific fraud, told me he used to view misconduct in Alzheimer’s research as rare, but has since gone through a “stages-of-grief process.”
“It doesn’t take that high a percentage of fraud in this discipline to cause major problems, especially if it’s strategically placed,” he added. “Patients ask me why we’re not making more progress. I keep telling them that it’s a complicated disease. But misconduct is also part of the problem.”
Exposing misconduct is the first essential, painful step for course correction, both to clean up the scientific record and to alert people to how compromised the field has become. Fixing a broken system — and accelerating the hunt for effective Alzheimer’s treatments — will also require new thinking about academic incentives and culture. One place to start: Train young researchers to value ethical conduct as the fundamental basis of science, and to hone their powers of skepticism. Advance them based on the quality rather than the quantity of their research products.
Government agencies that oversee Alzheimer’s research and enormously influence the field also need to rethink how they operate, and to move with urgency. Officials of the National Institutes of Health, of which the National Institute on Aging is a part, didn’t inspire confidence in response to the questions I sent them about Dr. Masliah as I conducted my 2024 investigation for Science. The N.I.H. acknowledged that the agency does not routinely check scientists’ work for fraud as part of the hiring process. “There is no evidence that such proactive screening would improve, or is necessary to improve, the research environment at N.I.H.,” said an agency spokesperson.
Hubris and lassitude about misconduct — shared by other funders and regulators, journals and universities — has to change. Alzheimer’s research must start self-policing effectively. That means journals and funders should invest more heavily in software tools and specialists to detect doctored images in article and grant submissions before they pollute the scientific literature. And it will require moving reviews of serious fraud allegations to experts outside an accused researcher’s home institution.
If the field’s institutional authorities fail to act, skeptics of science itself, most likely including those inside the Trump administration, surely will. Almost certainly, an ensuing overkill would describe ambiguity or innocent human error as fraud and eschew the thoughtful respect and due process needed to preserve what remains vital and true in neuroscience. That would enforce a new calamity on everyone who plans to grow old.