Another eminent neuroscientist hit with allegations of manipulation and fraud

Hundreds of Eliezer Masliah's publications on Alzheimer's and Parkinson's research have come under scrutiny.

Over the past two years there have been growing reports of fraud and manipulation in the field of neurodegenerative research, including a report from Science that one of the most pivotal studies in Alzheimer’s pathology, and a study that directed most of the funding in Alzheimer’s research towards the amyloid hypothesis, appeared to have doctored images which brought into question the actual findings of the study.

This comes on the heels of several different Alzheimer’s immunotherapies gaining fast-tracked approval even with limited data of clinical efficacy and concerning evidence of serious adverse events in the form of brain bleeds and brain swelling.

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In some ways these revelations are surprising due to the lucrative nature that is Alzheimer’s, dementia, and Parkinson’s research. One would expect that such a highly regarded field of research would be barred from such bad science. And yet, it’s this lucrative nature that is likely enabling many of the insidious malfeasance that is going on. There’s a lot to be gained to get an Alzheimer’s or Parkinson’s therapeutic to market, and there’s a lot of funding that gets granted towards this type of research especially as we continue to have an increasingly elderly population. Being at the forefront of this field carries with it a lot of renown when the public yearns for any sort of treatment to help their loved ones.

I’ve highlighted many of these issues regarding Alzheimer’s research because it embodies many of the issues we see in medicine/science where the science comes last, and the corporate greed comes first. More importantly, I’ve tried to highlight how people’s widespread ignorance can unintentionally lead to situations that encourage bad science to give the public something that they have no understanding of. Wanting a cure irrespective of the underlying research only helps to further drive questionable research.

As we become more critical of the medical and science field it becomes even more important that we understand and criticize things from an objective lens.

This takes us to the current revelations, all of which revolve around one researcher named Eliezer Masliah.

The following information will be a quick summary of some of Masliah’s work as well as the controversies. Note that all this information is coming to light through investigation from Science’s staff, as well as the investigation of many fraud sleuths such as Matthew Schrag, Yu Mang, and of course Elizabeth Bik who was pivotal in pointing out issues with the Alzheimer’s pathology paper that was recently retracted.

From Science

Masliah has had decades of research under his belt, and he’s considered to be one of the most prolific/cited researchers in the field of neuroscience, with a hand in many different organizations and institutions.

Here’s a short biography featured on the Michael J. Fox Foundation for Parkinson’s Research website:

Dr. Masliah received his MD in 1982, completed his residency in pathology at the National Institutes of Health in Mexico City in 1986 and a fellowship in neuropathology at the UC, San Diego in 1989. Dr. Masliah is currently professor at the Departments of Neurosciences and Pathology at UC, San Diego and director of the Autopsy Service at the UCSD-Medical Center. Dr. Masliah has published over 500 research articles. His laboratory investigates the molecular mechanisms of synaptic degeneration in Parkinson’s and Alzheimer’s diseases and is actively involved in developing novel treatments for these devastating disorders. Dr. Masliah’s laboratory was one of the first to develop a transgenic pre-clinical model for Parkinson’s and Alzheimer’s diseases and at identifying alpha-synuclein as a major contributor to the pathogenesis of these disorders. The Masliah laboratory is currently developing new treatment for Parkinson’s disease using small molecules that block accumulation of toxic alpha-synuclein in the brain.

This information seems outdated as Masliah appears to have authored nearly 800 papers. And what should interest readers more is the fact that Masliah was made director of the neuroscience division at the National Institute of Aging (NIA) in 2016 due to his work involving neurodegeneration.

Masliah’s work included examining the role of alpha-synuclein in the pathology of Alzheimer’s and Parkinson’s. Alpha-synuclein is a protein found within the presynapse of neurons and is involved in vesicle trafficking and release of neurotransmitters across synpases. Like with many neurodegenerative-related proteins, alpha-synuclein becomes a problem when misfolded forms of this protein aggregate.

From Calabresi, et al. Figure 1. Please refer to the original article for full information regarding the intricacies shown in the above figure. In short, the left image provides the typical mechanism by which alpha-synuclein operates by helping to shuttle molecules across the synapse. The right image illustrates how, due to various circumstances, alpha-synuclein may begin to misfold. Misfolded alpha-synuclein may then aggregate together forming what are called Lewy Bodies. The formation of these aggregates is argued to interfere with synaptic processes, and may result in loss of neuronal function and eventually neuron death. This results in many of the motor symptoms typically seen with diseases such as Parkinson’s.

It’s alleged that aggregation of these proteins results in synapse dysfunction and possible neuronal death through a possible immune/neuroinflammatory-mediated response.

This has resulted in research into therapeutics that aim to target these protein aggregates, with the idea that removal of these aggregates would attenuate some of the symptoms related to Parkinson’s Disease and Lewy Body Dementia.

Masliah’s work in this field has resulted in prospective therapeutics such as Prasinezumab, an IgG based monoclonal antibody intended to bind to alpha-synuclein and remove the protein aggregates in much the same way that many of the immunotherapies for Alzheimer’s is intended to bind to amyloid. He was also a pivotal player when it came to the therapeutic Cerebrolysin, which is a collection of neuropeptides derived from pig’s brain intended to mimic neurotropic factors¹- molecules which are key to the growth, survival, and differentiation of neurons.

Questions concerning Masliah’s body of work appears to have occurred over the past two years, and yet the degree of malfeasance may point to decades of systemic fraud. In fact, the fraud and manipulation seem so extensive that a nearly 300-page was created pointing out many issues in imaging pertaining to over 132 publications associated with Masliah, as highlighted in the excerpt from Science:

But over the past 2 years questions have arisen about some of Masliah’s research. A Science investigation has now found that scores of his lab studies at UCSD and NIA are riddled with apparently falsified Western blots—images used to show the presence of proteins—and micrographs of brain tissue. Numerous images seem to have been inappropriately reused within and across papers, sometimes published years apart in different journals, describing divergent experimental conditions.

After Science brought initial concerns about Masliah’s work to their attention, a neuroscientist and forensic analysts specializing in scientific work who had previously worked with Science produced a 300-page dossier revealing a steady stream of suspect images between 1997 and 2023 in 132 of his published research papers. (Science did not pay them for their work.) “In our opinion, this pattern of anomalous data raises a credible concern for research misconduct and calls into question a remarkably large body of scientific work,” they concluded.

NIH made a statement regarding these claims of fraud, mentioning that they examined two articles in particular which have been brought to their attention:

Following an investigation, the National Institutes of Health (NIH) has made findings of research misconduct against Eliezer Masliah, M.D., due to falsification and/or fabrication involving re-use and relabel of figure panels representing different experimental results in two publications. NIH will notify the two journals of its findings so that appropriate action can be taken. NIH initiated its research misconduct review process in May 2023 after it received allegations from the HHS Office of Research Integrity (ORI) that same month. NIH began its investigation phase in December 2023, concluded its investigation of these allegations on September 15, 2024, and notified HHS ORI of its findings.

It appears that Masliah is not serving as a director at the time the NIH statement was made, which doesn’t tell much regarding whether he was relieved of his position or whether he has not served a key role in the past months.

Even more surprising, the article mentions that Masliah’s work may not have been examined prior to his hiring, meaning that one of the largest institutions in the world responsible for overseeing the public’s health may have failed to do their due diligence in assessing Masliah for questionable work.

Masliah’s role as director, as well as his extensive body of work, means that Masliah carries a lot of influence in the type of research that gets conducted, as well as the type of research that gets funding:

As a division director, Masliah would hold sway over NIA’s neuroscience funding, according to Alan Leshner, who previously led two other NIH institutes and headed AAAS (publisher of Science) until 2015. In most cases, he says, institutes select grants based on scores awarded by peer-review “study sections.” But institute and division directors can fund preferred projects, such as studies of amyloid, the brain protein linked to Alzheimer’s disease, over better scoring competitors.

“There’s no question that in most cases, a division director … is viewed as someone who has the judgment to set priorities,” Leshner says. They can also alter the direction of a field. If a division director shows interest in a particular aspect of neuro-science related to aging, he adds, “you get [many] proposals in the next round in that area.”

After all, it was Masliah’s research that appears to have helped Prasinezumab get approval for clinical trials:

Masliah’s work, for example, helped win a nod from the U.S. Food and Drug Administration (FDA) for clinical trials of an antibody called prasinezumab for Parkinson’s. 

It’s important to note that there is no clear evidence that Masliah used his role as director to divert funding or to direct research endeavors to specific areas. As of now any of these claims are to be considered purely speculative. Nonetheless, one can’t help but question if such an act could have occurred given the current circumstances. Again, there is much for Masliah to gain by producing fraudulent images, and so it’s rather difficult to decouple Masliah’s role as director with the belief that he may have some self-serving intentions in his role.

There’s a lot to this story that will come to light in the future, and I will try to cover this story as it continues to develop. But in the meantime, I encourage readers to read the Science article for themselves to get a better understanding of what is known.

In general, it’s scary to think how much of what we know in science may just be built on lies and misinformation. Science, and especially neurodegenerative research, is in a very precarious position in which trust in such fields continues to erode. But it’s not as if this erosion is coming out of the blue- science institutions continue to show that they are focused more on prestige and money than they are regarding fruitful scientific endeavors. There’s an obvious lack of integrity that pervades much of the research that is being conducted.

If scientists want to gain better trust with the public there needs to be greater humility, greater, transparency, and be more open to criticizing bad science and calling out bad actors.

And if people want better science, they must have more realistic expectations for what science is capable of, as well as an understanding of what research is going on. It’s within these areas of obscurity where scientists with ill-intent can flourish as an ignorant public is unable to discern good science from bad.

We need to understand science better to get better science in turn.

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Photo by Robina Weermeijer on Unsplash

Additional readings for those interested:

• I stumbled across an article from the website For Better Science which appears to have covered a good deal of the controversy around Masliah starting all the way back to early 2023. This seems like a good read for those who want an additional look into some of the controversy, the images, and questions from researchers.

• Calabresi, et al.²: Alpha-synuclein in Parkinson’s disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction.

• Stefanis, L.³: α-Synuclein in Parkinson's disease. 

• Tolosa, et al.⁴: Challenges in the diagnosis of Parkinson's disease.

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1. Severini C. (2022). Neurotrophic Factors in Health and Disease. Cells, 12(1), 47. https://doi.org/10.3390/cells12010047

2. Calabresi, P., Mechelli, A., Natale, G. et al. Alpha-synuclein in Parkinson’s disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction. Cell Death Dis 14, 176 (2023). https://doi.org/10.1038/s41419-023-05672-9

3. Stefanis L. (2012). α-Synuclein in Parkinson's disease. Cold Spring Harbor perspectives in medicine, 2(2), a009399. https://doi.org/10.1101/cshperspect.a009399

4. Tolosa, E., Garrido, A., Scholz, S. W., & Poewe, W. (2021). Challenges in the diagnosis of Parkinson's disease. The Lancet. Neurology, 20(5), 385–397. https://doi.org/10.1016/S1474-4422(21)00030-2