Is Most Neurodegenerative Research Based on Fraudulent Data?
The recent Masliah scandal and other fraud revelations force the neurodegeneration field to confront a chilling question: how much of its foundation is built on manipulated data?
Neurodegeneration research promises hope for millions, but recent controversies reveal a troubling side. The fraud and misconduct cases by Eliezer Masliah, Sylvain Lesné, and Marc Tessier-Lavigne, have cast a gloomy shadow over the field.
As the allure of high-impact breakthroughs collides with the demand for scientific accountability, it’s worth asking: How deep does this problem go?
In this post, I’ll unravel these three stories, and explore their impact on the field.
Masliah: A Fall from Grace That Shakes the Foundation
Eliezer Masliah, a name once synonymous with cutting-edge neurodegenerative research, now evokes a darker association: research misconduct on a massive scale. As the former head of the Division of Neuroscience at the National Institute on Aging (NIA), Masliah’s career was punctuated by pioneering work on AD and Parkinson’s disease (PD), particularly around the alpha-synuclein protein. But behind this illustrious facade lay a 26-year legacy of doctored data, as revealed by an investigative report from Science and a damning NIH statement released just days apart.
The allegations center around image manipulation, a common but insidious form of scientific fraud.
A 286-page dossier compiled by image analysts highlights 132 papers riddled with duplicated, spliced, or relabeled figures. Micrographs reappear with altered captions; Western blots are cut, pasted, and patched to fit desired narratives. The scope of manipulation (stretching across decades and involving over 550 co-authors) has left the neurodegenerative research community stunned.
The repercussions of Masliah’s misconduct ripple far beyond academic journals. Fundamental studies from his lab underpin clinical trials for at least three experimental therapies:
Prasinezumab: An alpha-synuclein-targeting antibody by Prothena and Roche, which recently missed its primary endpoint in a Phase 2 trial (the second time it misses it). Was this a product of flawed science from the start?
Minzasolmin (UCB0599): A drug co-developed by Neuropore, a company Masliah co-founded, and UCB. This alpha-synuclein misfolding inhibitor recently failed in a Phase 2 trial.
I discussed the recently failed prasinezumab and mizasolmin Phase 2 trials in a previous post:
Cerebrolysin: A porcine-derived peptide mixture marketed in Russia and other countries but not approved in the U.S. or EU. Eight of Masliah’s studies supporting its efficacy are implicated in the scandal.
The NIH has since removed Masliah from his leadership role following an investigation initiated in May 2023. Critics argue that the NIH suffered of systemic lapses in oversight, especially given Masliah’s high-profile position. Could an early audit of his work have prevented this debacle?
The fallout has been swift but incomplete. Co-authors scramble to distance themselves, institutions remain tight-lipped, and the NIH faces congressional scrutiny for failing to ensure transparency and accountability.
The neurodegeneration community confronts a chilling question: how much of the field’s foundation rests on manipulated data?
The tragedy of this saga is multifold. Honest collaborators and trainees are now tainted by association.
Patients and families pinning their hopes on therapies like prasinezumab and mizadolmin are left with uncertainty - they wasted many years of their lifes participating in these trials.
And the trust in neurodegenerative research, a field already fraught with challenges, has taken a significant hit.
Sylvain Lesné: The Star That Fizzled
If the AD research world were a dramatic stage play, Sylvain Lesné would be cast as a meteoric star whose brilliance masked troubling shadows.
In 2006, Lesné, then working in Karen Ashe’s lab at the University of Minnesota, published a Nature paper that identified a novel amyloid-beta (Aβ) oligomer, dubbed Aβ*56 (pronounced “A-beta star 56”), “as a toxic culprit driving cognitive decline”. This discovery was heralded as groundbreaking. Aβ*56 seemed to provide a smoking gun for the amyloid hypothesis, the dominant theory linking Aβ aggregation to AD.
The accolades came quickly: Ashe won the prestigious Potamkin Prize, and the paper became one of the most-cited Alzheimer’s studies of the 21st century. NIH funding for amyloid oligomer research skyrocketed, from almost nothing in 2006 to $287 million annually by 2021.
But there was a catch: Aβ*56 may never have existed.
In late 2021, neuroscientist and physician Matthew Schrag was drawn into a separate investigation of potential misconduct involving Cassava Sciences, a biotech firm behind the experimental Alzheimer’s drug simufilam.
I discussed the Cassava scandal in a previous post:
Schrag’s sleuthing led him to PubPeer, an online forum where scientists discuss potential errors in published research.
There, Schrag identified manipulated images in 20 of Lesné’s papers, with 10 focusing on Aβ*56. Western blot bands were duplicated, composite images seemed stitched together, and some figures were recycled across publications as if they were fresh data.
Science’s investigative journalists corroborated these findings, enlisting experts like Elisabeth Bik, a molecular biologist and forensic image consultant, who described the manipulation as “shockingly blatant.”
What made this discovery particularly explosive was its implications for AD research. The original Nature paper wasn’t just another study, but a cornerstone for years of amyloid research.
Lesné’s fraudulent data didn’t merely mislead scientists; it misdirected research and funding. The amyloid hypothesis faced new scrutiny as one of its supporting pillars crumbled. Compounding the issue was Cassava Sciences, which had built much of its simufilam claims on amyloid-related mechanisms. Schrag’s discoveries raised questions about the integrity of research underpinning their drug’s development.
For investors, analysts, and regulators, the revelations about Lesné’s work are a sobering reminder of how fragile the scientific foundation of drug development can be. If fraudulent data shaped the trajectory of amyloid research for nearly two decades, what does that mean for drugs like Simufilam? And what does it say about the peer-review system that failed to catch such glaring errors?
The immediate consequences of the Lesné scandal are grim. Journals like Nature issued “expressions of concern” on several papers, while NIH and the University of Minnesota launched investigations. But the fallout extends beyond academic journals.
For the broader AD research community, the revelations have cast a pall over the oligomer hypothesis. While most researchers insist that oligomers remain a valid target, the damage to the field’s reputation is undeniable.
This isn’t just about one paper or one protein, it’s about trust in the scientific process.
It is important to highlight that the amyloid hypothesis isn’t invalidated. Approved drugs such as lecanemab and donanemab do remove amyloid plaques very effectively and do result in some clinical benefit in patients with early symptomatic AD (more details on this in one of my previous posts).
However, this scandal underscores the need for rigorous scrutiny in research and journal publication processes.
Marc Tessier-Lavigne: From "Miracle Result" to Resignation
Marc Tessier-Lavigne, biotech executive and former Stanford president, once stood poised to reshape the AD field with a “groundbreaking” 2009 Nature paper. The study, co-authored during his tenure at Genentech, proposed a novel mechanism of neurodegeneration involving the binding of a protein fragment (N-APP) to a receptor (DR6).
At the time, it was heralded as Nobel-worthy, garnering over 1,200 citations and inspiring patent filings.
But the “miracle result” turned into something else. Internal reviews within Genentech revealed that attempts to replicate the findings failed, prompting whispers of manipulated data. Multiple scientists alleged falsification, with one recalling being told explicitly that “lab data had been falsified.” By 2011, drug discovery programs based on the study were abruptly halted, and related patent applications abandoned.
Tessier-Lavigne has consistently denied any wrongdoing, maintaining he was unaware of an investigation and categorically rejecting claims of a cover-up.
However, scrutiny of his broader body of work deepened in 2023 when allegations of data manipulation surfaced across multiple papers he co-authored.
On July 19, 2023, following a review led by the Stanford Board of Trustees, Tessier-Lavigne announced his resignation as Stanford’s president, effective August 31. The committee concluded there was “manipulation of research data” in at least four of five papers under review (final report here). While Tessier-Lavigne himself was not found guilty of direct misconduct, he did acknowledge responsibility as a senior author and moved to retract or correct the affected papers.
Even as controversies swirled, Tessier-Lavigne’s professional momentum seemed unfazed. He co-founded Denali Therapeutics and became CEO of Xaira Therapeutics, leveraging his scientific prominence to build biotech companies dedicated to tackling neurodegenerative diseases. These ventures capitalized on his reputation as a pioneer in AD research, an image tarnished by the fallout from both the Nature study and the other publications with manipulated data.
The contrast between the promise of Tessier-Lavigne’s research and the reality of its collapse is as stark as it is sobering. It raises hard questions about how biotech advances are validated, the role of leadership in scientific accountability, and what happens when science veers from rigor into illusion.
Conclusion
While it would be hyperbolic to claim that all neurodegeneration research rests on a foundation of fraud, it would be equally naïve to ignore the instances where scientific integrity has faltered. The cases of Masliah, Lesné and Tessier-Lavigne highlight how groundbreaking claims can captivate the field, influence careers, and redirect vast sums of funding, only to crumble under scrutiny years later.
These three episodes force us to confront uncomfortable questions:
How much more fraud or misconduct lies hidden in the shadows, shielded by prestige, institutional inertia, or the sheer complexity of biomedical research?
What promising avenues of investigation have been abandoned due to the ripple effects of faulty studies?
And perhaps most crucially, how can the scientific community better safeguard against these breaches while maintaining the trust that science so deeply relies on?
For those invested in neurodegeneration research, these stories are both a cautionary tale and a rallying cry. They underscore the urgent need for transparency, replication, and accountability in a field where the lives of millions hang in the balance.
Readers - What is your thoughts on these fraud cases? Please share your thoughts, questions, and experiences in the comments below!
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Views expressed here are my own and not necessarily those of my employer. All data mentioned and discussed are publicly available.