#neuropathologist

[fidicusraredisease]

Call : +917997101303 | Whatsapp : https://wa.me/917997101505 | Website : https://fidicus.com

Changes in the body due to SSPE, Subacute Sclerosing Panencephalitis | Treatment Cure Relief | Rare Orphan Unique Disease | Dr. Bharadwaz

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About Video : In this video, we delve into the pathology of Subacute Sclerosing Panencephalitis (SSPE), a severe neurological disorder caused by a persistent measles virus infection. Learn how the virus affects the brain, leading to inflammation, nerve cell degeneration, and the progressive decline of cognitive and motor functions. We'll explore the stages of the disease, the microscopic changes in brain tissue, and the latest research aimed at understanding this devastating condition. Join us for a comprehensive look at SSPE pathology.

[l3irdl3rain]

After several months I’ve finally received Duncan’s necropsy report. I’m so thankful for everyone who donated to allow me to get Duncan to the neurologist. As well as thankful to UW Madison for making the entire experience as painless as possible.

“I apologize for the delayed communication. The results of Duncan's finalized necropsy results have returned. I attached the full report for you, if you would like to read through it. Multiple neuropathologists were consulted on his case, due to the abnormalities found.

Your sweet little man had degenerative conditions as the cause for his signs.

The first noted change was cerebellar abiotrophy. This is different than cerebellar hypoplasia. Cerebellar hypoplasia occurs when an animal is born with a smaller than normal cerebellum, and they generally do not have any progressive cerebellar type signs. However, cerebellar abiotrophy is a degenerative condition where animals are born with a normal sized cerebellum, and then with time and age, it degenerates, with the normal cells of the cerebellum dying off and the cerebellum as a whole becoming smaller. Cerebellum abiotrophy is not a terribly common entity in cats.

The second change that was noted was degenerative changes to his spinal cord. In combination with the degenerative changes to his cerebellum, he had what is termed spinocerebellar degeneration. This is just an umbrella term for both degenerative changes to his cerebellum and spinal cord.

While we do not know the exact underlying cause as to why Duncan had these degenerative changes to his cerebellum and spinal cord, it could have been due to a storage disease, from an infection in utero, or secondary to a genetic mutation that he was born with. No matter the underlying cause, with time and age, his signs would have absolutely continued to progress in severity.

While I know the decision was not an easy one for you, I think you did the most selfless thing by considering Duncan's quality of life and euthanizing him.

I also wanted to thank you for allowing us to perform a necropsy on him, and for us to learn more about this condition.”

[kleinewahines]

"Well, the slang term is that, anyway," she said, eyes twinkling a little with barely suppressed mirth. Then, her accent thickening audibly, "We call it the olecranal skin in my line of work. Also fun fact, it can't really feel a lot of pain because our pain receptors aren't distributed as thickly there as the rest of your body. You can pinch and pull that area much as you like, it won't complain to your brain. That's not to be confused with the ulnar nerve pain you get if you hit your elbow just right -- or wrong, depending on your point of view -- on something."

A smile then. "I bet if someone were to come up with something better than patella posterior they would get a lot of acclaim." Because there wasn't really money in naming things. Just fame.

@kleinewahines : "Did you know there's actually NO proper name for the back of the knee? They just call it the posterior of the knee. I think someone should make one up." -Micah

"they can make a name for the skin of your elbow, but not the back of the knee? humanity sure has weird as hell priorities."

"...the skin on your elbow is called a wenis, if you're wondering."

[justisabellethings]

Don’t you guys find it funny that Helena Riggs was a real person in history, a celebrated neuropathologist?

And Severance is a show about jamming a chip in your brain? Which of course, could mean nothing.

And that the town of Kier was cut off from the world in the 1930s, which is why it’s so behind on technology? And Helena Riggs was most active during that time frame?

Anyways… Could mean nothing.

[unhonestlymirror]

Harvard Ophthalmology Professor and Eye Surgeon from Lithuania:

Ūla Jurkūnas

"As Ū. Jurkūnas explains, at Harvard only 11% of professors have a so-called tenured position. 30% of them are women.

"[...]We all love Lithuania so much. It seems to me that we, Lithuanians, are especially attached to Lithuania, its nature, its smell. And I had to leave when I was young, it was a rather traumatic event in my life. This achievement [becoming a Harvard professor] makes me feel that I left for a reason. My mother, who took me there, created this opportunity for me in the field of science and medicine,” the interviewee shares her thoughts.

Although Ū. Jurkūnas admits that throughout her years of work she has seen that perhaps her male colleagues reach higher ranks faster, she focused on her own goals.

"I've seen myself my whole life simply as someone who has certain interests and certain goals. I've never looked at myself as whether I'm a woman or whether I'm a man."

The interviewee says she has always been attentive to details and loves meticulous work, which is why she became interested in eye surgery, where she has to operate under a microscope. The Lithuanian, who works at the clinic three days a week, sometimes performs up to 12 operations in one day. The remaining two days she devotes to scientific work and meets with students in the laboratory.

"You just do the things you need and want to do, things that are interesting to you. I think it's very important to never feel too much of a victim, that is too hard for me. The most important thing is to look at the goal and go your own way. Then, I think you'll succeed anyway," the professor assures.

"My mother always showed me that as a woman you are also an individual who must achieve your goals. My mother's education was a very important influence," says the interviewee. "But specifically, I was inspired to go into medicine by my father, who is a neuropathologist in Vilnius. He is very good at working with patients. I think he inspired me to understand the patient's side and how to be a doctor. And for the scientific field, I think I was inspired by my grandfather, who was a chemist and a member of the Academy of Sciences in Vilnius."

"My dream is to make discoveries in the laboratory reach people, change the human condition, and heal them. I am very grateful to my family for their support, for working at this Harvard hospital, one of the largest eye hospitals, where I see patients not only from all over America, but from all over the world. They come with diseases that other doctors may no longer know how to treat, or have treated but failed. I am the one who performs surgeries and helps people. The fact that I am a professor is not even as important as what I do here," says the interviewee.

Several years ago, Dr. Jurkūnas, along with a group of other doctors, performed the first corneal cultured stem cell transplant in America. This was a major achievement, allowing blind patients to regain their sight. The Lithuanian is pleased that the final results of research on cultured stem cell transplantation will soon be published in the prestigious scientific journal Nature Communications.

"For example, we are now aiming to apply the use of those stem cells to a wider group of patients, because so far it is only possible for very specific cases where the disease is in one eye. Then we take stem cells from a healthy eye, grow them in the laboratory and transplant them into the affected eye. We want to make it so that if both eyes cannot see, we could grow those stem cells using a donor. That is our next project. There are many steps to take from scientific discoveries to implementation and treatment."

As Ū. Jurkūnas says, she considers herself both Lithuanian and American and feels comfortable in both countries.

"Maybe that's why I feel good in America, because I have my own professional life, I don't try to compare myself to someone all the time. And I'm like many other people in America, because there are a lot of immigrants in medicine and academia. In Lithuania, sometimes people say: "Oh, Americans came here." But I feel Lithuanian just the same. That's why I'm very grateful that you, the Lithuanian press, are interested in my achievement, even though it's in America," says the interviewee.

During those 35 years at the Atlantic Council, Jurkūnas says she has watched Lithuania grow. She assures us that it is always wonderful to return to this charming and prosperous European country."

(c) full LRT article.

[guzhufuren]

came to a new massage place that opened up near my building.. asked them to fix my spine the way my neuropathologist used to without any massage🧍‍♂️ now i'm sitting here listening to weird sounds of other people getting massaged.. sounds the same as that one guy's video of massaging and washing and cleaning up a guy extremely intensively, you know the one

[gelato444]

work was literally hard today. What a concept. It was good hard. I had to solve puzzles basically. so we send brains to the neuropathologist to diagnose them (in the case of natural deaths) and when we get the brain back it’s a fucking mess just absolutely torn to shreds, and my job is to go through the shreds and find regions for people who want the samples. so I had to like reconstruct the brain with a bunch of fixed slices like it was a puzzle, like following lines and textures of the brain and structures inside. ok I’m done dorking out lol. but it was really cool and hard

[ozziesjester]

papa soup is a neuropathologist, and i think mama soup died of early onset sporadic creutzfeldt-jakob disease. he probably spent a lot of time trying to figure out how to slow the progression of prion diseases when she was diagnosed and took an extended leave of absence before deciding to move to south park after her passing

[292-ludovica]

are there like. neuropathologists/epidemiologists specialising in proteopathies on here

I crave Information

[kleinewahines]

V: Orthrus (i'm being lazy again)

Mass Effect Verse

Vi Commander Vi Shepard. Colonist, sole survivor. Soldier. No biotics to speak of and doesn't want them. Actually really fucking hates being around biotics due to an event early in her military career (commiserating with Vega on this is a huge source of comfort for Vi). 'Lost' Powder on Mindoir.

Micah Tasked with helping those who left Cerberus for whatever reason, she makes sure everyone's health is on the up and up. Because of her neurology training, she helps the almost Indoctrinated the most. Is involved only slightly in the Crucible Project, if only because there isn't much cause for a neuropathologist on such an engineering project. She is just meant to track peoples' neurology to search for any Indoctrinated saboteurs.

Jessie Biotic and loving it. She stole the latest amp coming out of the company she works for and nobody knows it and she lies on all her forms about which amp she has. Ostensibly is only in biotic research anyway, has no contract or contact with the Alliance. As with Micah, no work with the Crucible.

Kath N7 Marine a few years before either Leng or Shepard were in the program but after the First Contact War. During an assignment, was exposed to demozane in an explosion which broke a number of bones from the chest down. Is technically retired now but does work security for the Crucible Project.

[notalostcausejustyet]

One of my favorite fic authors is a neuropathologist. There are at least two librarians, one psychologist and one wildlife research specialist in the group too. So. Many. SMART and accomplished people write fic. So many.

I just found out one of my favorite AO3 authors of all time is a fucking neurosurgeon which was surprising initially just because I often forget AO3 writers are real people and not smut angels sent down from the heavens to make us feel alive, but in hindsight it makes perfect sense.

they are a fucking genius so. they just apply that genius to multiple fields.

[jbrunsolved]

Head trauma vs strangulation - In which order? Also, there is no evidence of chronic SA.

From Woodward, 2021: "In an interview with me Dr. Meyer said, “They are as close as happening simultaneously as I’ve seen. Enough so that I didn’t know which happened first and listed them together as that’s the most accurate.”

-Woodward, Paula. Unsolved: The JonBenét Ramsey Murder 25 Years Later

"Read Dr Lucy Roarks timeline. She was a pediatric neuropathologist who examined slides of Jonbenets brain. Pretty convincing once you read her credentials"

Read Dr Lucy Roarks timeline.

Rorke. She never examined anything other than slides. She was brought in by the BPD for the GJ investigation.

Like Donald Foster, Lucy was hired to present a BORG supporting report. It's as simple as that.

Use common sense. The blow to the head woukd have rendered her unconscious immediately - she would not have been able to fight a garrote put on her later. And if she had been hit in the head without the garrote being in place already, there woukld have been a LOT of bleeding inside the skull. There wasn't much blood inside and she didn't even have a BUMP visible to the coroner. He was unaware of the head injury until he opened her scalp himself.

The hired witness was playing a role. And in a grand jury, the persecutors are NOT limited to telling the truth, the whole truth and nothing but. They can slant the evidence in outrageous ways. (Personally I find that appalling.)"

This finishes it for just about every RDI theory

I’ve been saying for ages that the head blow and strangulation were simultaneous events. Now it has been confirmed by Woodward that this is what the coroner himself says.

The cause of death listed two reasons for her death: asphyxia by strangulation associated with craniocerebral trauma. Simply put, she was killed by strangulation and a blow to the head. In an interview with me Dr. Meyer said, “They are as close as happening simultaneously as I’ve seen. Enough so that I didn’t know which happened first and listed them together as that’s the most accurate.”

Woodward, Paula. Unsolved: The JonBenét Ramsey Murder 25 Years Later (p. 66). City Point Press. Kindle Edition.

Are there any RDI theories that don’t rely on there being at least 45 minutes between the head blow and the strangulation?

Autopsy reveals new details By Mary George and Ann Schrader Denver Post Staff Writers

July 15 - JonBenet Ramsey was the apparent victim of an "explosion of rage," but one can't conclude that she was the victim of sexual assault, said medical experts who reviewed additional portions of her autopsy report released under court order Monday.

The full autopsy report, which could lead medical examiners to other conclusions, still has not been released. The remaining brief six sections of the report will be released Aug. 13.

The new information, which had been sealed for nearly six months, describes the 8.5-inch-long fracture on the right side of JonBenet's head, the deep furrow left around her neck by the cord used to strangle her and injuries to her genital area.

"I would guess there was an explosion of rage . . . that led to this death," said Dr. Richard Krugman, dean of the University of Colorado School of Medicine and a nationally known child-abuse expert.

Evidence of "mild trauma" around the vagina "is not diagnostic of sexual abuse," Krugman said. The vaginal injuries can be caused by trauma such as an infection, irritation from a bubble bath or in connection with abuse.

About three months ago, Krugman was asked by Boulder District Attorney Alex Hunter to consult on the Ramsey case. He studied the full autopsy report and several other documents.

Krugman said he told Hunter basically what he said Monday, that "there is nothing here that is specific that this was a child who was sexually abused." Instead, Krugman said, "I see a child who was physically abused and is dead."

Dr. Todd C. Grey, chief medical examiner for the state of Utah, had other observations on reading the autopsy report.

"The strangulation is probably the last event," Grey said. "The pattern of injury to her neck and the hemorrhaging indicates she's alive at the beginning of that process. "This wasn't a gentle killing. This kid was fighting."

Attorneys for JonBenet's parents, John and Patsy Ramsey, issued a statement Monday. "We have not had the opportunity to review the autopsy report, but credible experts have confirmed what we have been saying all along - that there is no evidence of abuse or molestation prior to the night of her murder."

The physical abuse was evidenced, Krugman said, by the severe brain injury and that she had been strangled.

Most of the injuries appear fresh, and Krugman said he has "not had information" nor is there anything in the autopsy report that indicates a history of abuse.

"The problem in abuse cases when a child dies in the middle of the night when there are several adults around, (is that) it's impossible to tell who did it," he said. JonBenet Ramsey was found strangled in the basement of her Boulder home about 1:20 p.m. last Dec. 26. Early that morning, her mother found a ransom note demanding $118,000 for JonBenet's safe return.

Boulder County Coroner John Meyer arrived at the house that evening at about 8, according to information released Monday. He went into the house about 8:20 p.m., examined the body and left by 8:30 p.m.

Meyer fought release of the autopsy report, arguing that it would harm the investigation. The coroner won an initial court ruling sealing the autopsy.

But when the seal came up for renewal on May 15, District Judge Carol Glowinsky ordered most of the rest of the report opened. And even the six remaining sealed portions would be released 90 days later, Glowinsky ruled.

Meyer and Deputy County Attorney Madeline Mason appealed the decision to the Colorado Supreme Court. On Monday, the high court declined to review the case. Mason announced she wouldn't continue the appeal. Glowinsky then released the information.

Boulder police detective Cmdr. John Eller remained noncommittal about whether the late release of the additional autopsy report portions will affect the investigation.

"Time will tell if it's had an impact or not," Eller said. "Clearly our position is that it would, and that is why we've taken steps to protect it for as long as we could."

Other medical examiners said Meyer was extremely thorough in his autopsy.

Dr. Tom Henry, chief medical examiner for the city of Denver, said that among the most revealing aspects of the data released Monday are the injuries around JonBenet's neck and head.

"Now you have some idea of the extent of the fracture," he said. "You now know it goes the whole length of the side of the head."

In another development, Eller said the investigation into a breakin of the Ramsey case file at the county department of social services was "for the most part concluded" and that no one would be criminally charged in the breach.

"Best we can tell, it was someone curious trying to get into the file," Eller said. "We presume they were successful, but there's really no way to tell."

Family spokeswoman Rachelle Zimmer said the Ramseys had not reviewed the newly released information, "but credible experts who have confirm what we have been saying all along _ that there is no evidence of abuse or molestation prior to the night of her murder."

[reasoningdaily]

Science: Did a top NIH official manipulate Alzheimer's and Parkinson’s studies for decades?

In 2016, when the U.S. Congress unleashed a flood of new funding for Alzheimer’s disease research, the National Institute on Aging (NIA) tapped veteran brain researcher Eliezer Masliah as a key leader for the effort. He took the helm at the agency’s Division of Neuroscience, whose budget—$2.6 billion in the last fiscal year—dwarfs the rest of NIA combined.

As a leading federal ambassador to the research community and a chief adviser to NIA Director Richard Hodes, Masliah would gain tremendous influence over the study and treatment of neurological conditions in the United States and beyond. He saw the appointment as his career capstone. Masliah told the online discussion site Alzforum that “the golden era of Alzheimer’s research” was coming and he was eager to help NIA direct its bounty. “I am fully committed to this effort. It is a historical moment.”

Masliah appeared an ideal selection. The physician and neuropathologist conducted research at the University of California San Diego (UCSD) for decades, and his drive, curiosity, and productivity propelled him into the top ranks of scholars on Alzheimer’s and Parkinson’s disease. His roughly 800 research papers, many on how those conditions damage synapses, the junctions between neurons, have made him one of the most cited scientists in his field. His work on topics including alpha-synuclein—a protein linked to both diseases—continues to influence basic and clinical 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.

Neither Masliah nor the various drug companies, universities, or federal ­agencies that were provided the dossier have so far rejected or challenged any of its examples of possible misconduct despite being given the material more than 2 weeks ago. And today, the National Institutes of Health (NIH) released a statement saying that following an investigation, it had “made findings of research misconduct” against Masliah for “falsification and/or fabrication involving re-use and relabel of figure panels” in two publications. According to the statement, Masliah no longer serves as NIA’s neuroscience division director, but NIH declined to further clarify his employment status.

Masliah and Hodes, via a spokesperson, declined to reply to detailed questions, provide an interview, or comment on the dossier. NIH Director Monica Bertagnolli also declined to comment. And Masliah did not reply to Science’s requests for raw images and other data related to the examples in suspect papers, or to a new request for comment on the NIH misconduct finding.

The dossier challenges far more studies than the two cited in NIH’s statement, including many that underpin the development and testing of experimental drugs (see sidebar). 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. Made by Prothena—a company backed by big money—the drug is intended to attack alpha-synuclein, whose build up in the brain has been linked to the condition’s debilitating physical and cognitive symptoms.

But in a trial of 316 Parkinson’s patients, reported in 2022 in The New England Journal of Medicine, prasinezumab showed no benefit compared with a placebo. And volunteers given infusions of the antibody suffered from far more side effects such as nausea and headaches than those in a placebo group who received sham infusions. Prothena is now collaborating in another trial of the drug candidate involving 586 Parkinson’s patients.

The creators of the dossier, who were unaware of NIH’s probe when they spoke with Science, emphasize that they are not themselves accusing Masliah or his colleagues of fraud or misconduct. They note that some of the identified image problems might have been simple errors, and that when images are prepared for publication, some can acquire innocent visual artifacts that resemble improper changes. Distinguishing the two sometimes requires comparison to raw, high-resolution images and other data, which the dossier’s authors did not have. But they say their findings merit formal investigations.

The enormity of apparent problems described in the Masliah dossier stunned 11 neuroscientists who agreed to review it for Science. “Breathtaking,” says neuroscientist Christian Haass of the Ludwig Maximilian University of Munich. “People will, of course, be shocked, as I was. … I was falling from a chair, basically.”

He and the other researchers didn’t personally verify every example of possible misconduct, but they agreed that most of the suspect work cannot reasonably be explained as careless errors or publishing anomalies. “I’m floored,” says Samuel Gandy, a prominent neurologist at the Mount Sinai Alzheimer’s Disease Research Center who was visibly shaken during a video interview. “Hundreds of images. There had to have been ongoing manipulation for years.”

Gandy was disturbed, for example, that Masliah and colleagues seem to have used the same image of a mitochondrion, a cellular energy-producing structure, in two articles on different topics published 2 years apart in different journals. “The bus driver could see that they are identical,” Gandy says.

MASLIAH IS THE SOLE common author on every paper in the dossier, usually taking the first or last position in multiauthor articles. Those positions imply he did the majority of the publication’s work or bears primary responsibility for it, although the others contributed.

Several of the neuroscientists who reviewed the dossier say it seems implausible that Masliah was duped by a colleague. “Given the extended time frame and huge number of differing collaborators and co-authors on these papers, [possible misconduct] by a rogue postdoc or a collaborating scientist doesn’t apply here,” says Tim Greenamyre, director of the University of Pittsburgh Institute for Neurodegenerative Diseases. “I have a hard time believing that he didn’t know, whether he changed the images himself or somebody else did so on his behalf.”

I’m floored ... Hundreds of images. There had to have been ongoing manipulation for years.

Samuel Gandy

Mount Sinai Alzheimer’s Disease Research Center

At a minimum, according to neuroscientists who spoke with Science, the large volume of doubtful images erodes trust in Masliah’s overall body of work. All 11 who reviewed the dossier agree that all his problem papers should be investigated by NIH, scholarly journals, funders, and UCSD. The university declined to comment, and NIH did not say whether it planned or was conducting a broad misconduct investigation into his research. Masliah this week, days after NIH said it concluded its probe, still appeared with Hodes, the NIA director, to give introductory remarks at the start of a national Alzheimer’s summit on the NIH campus.

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.”

There’s no evidence that Masliah has been a poor steward of NIA’s neuroscience budget or directed it down blind alleys underpinned by suspect data, but NIH’s statement today still leaves many crucial questions unaddressed.

“The volume of papers and resources involved are enormous—as is Dr. Masliah’s leadership and influence on the field, including drug development pipelines,” says Vanderbilt University neuroscientist Matthew Schrag, one of those who helped assemble the dossier. “That makes it a very influential example of possible misconduct.”

MASLIAH, 65, TRAINED in medicine and neuropathology at the National Autonomous University of Mexico (UNAM), earning his medical degree in 1982 and completing a residency in pathology in 1986. He married a U.S. resident who also studied medicine at UNAM. They relocated to San Diego after Masliah’s training.

Soon after, he landed a plum research fellowship in the lab of Robert Terry, a titan in neuropathology and Alzheimer’s research who reportedly received NIH’s first grant for the neurodegenerative condition in the 1960s. “I was incredibly lucky to meet Dr. Bob Terry,” he told a UCSD interviewer in 2016. In a 1990 photo of Terry’s lab staff, a dark-bearded, youthful Masliah stands proudly, arms folded and wearing his trademark large glasses, beside his famous mentor, who died in 2017. Terry and Masliah pioneered the use of an optical imaging method known as confocal microscopy to create high-resolution 3D images of brain cells.

Masliah went on the lead UCSD’s Experimental Neuropathology Laboratory, where he contributed to early work on alpha-synuclein and novel antibody and vaccine approaches to attack Alzheimer’s and ­Parkinson’s—some of which led to experimental drugs such as prasinezumab that have reached human trials. For Parkinson’s, he also explored antidepressants, and anti-inflammatory drugs or compounds. And for Alzheimer’s, he looked into compounds to decrease the production of amyloid, which builds up in the brain and forms deposits known as plaques outside neurons.

Neurologist Douglas Galasko, who formerly directed the UCSD Alzheimer’s Disease Research Center, where Masliah worked, praises his scholarship and character, calling him “highly collegial and very hardworking.” Galasko co-authored five papers in the dossier, making modest contributions unrelated to apparently doctored images. (He opted not to view the document.)

Galasko says he never heard concerns or doubts about Masliah, whom he describes as “very serious, yet warm and thoughtful, and engaging to have a conversation with.” Those qualities earned him long-term loyalty from investigators working in his lab, Galasko adds. “He’s a very effective spokesperson, organizer, and synthesizer of ideas.” Colleagues at UCSD, he notes, felt enormous pride when Masliah took the helm at NIA’s neuroscience division.

Major impact

Eliezer Masliah’s research on Parkinson’s and Alzheimer’s diseases has enjoyed global influence. His output, as well as the number of citations to his papers, place him among the world’s top 10 scientists in certain subfields (highlighted in red).

“NIA sets the agenda worldwide for age-related diseases,” says Scott Ayton, who directs a neuroscience center at the Florey research institute in Australia, echoing peers in the U.S. and Europe. He was among those who reviewed the dossier and considered the concerns highly credible.

University of Texas at San Antonio neuroscientist George Perry, chief editor of the Journal of Alzheimer’s Disease, describes Masliah’s research as influential and well-regarded, as do other experts in neurodegenerative diseases. In key topics related to Alzheimer’s and Parkinson’s, Masliah frequently ranks in the global top 10 researchers—and often first—by number of papers and citations to them, according to an analysis of data from Dimensions Analytics, a scholarly research data bank from the U.K. company Digital Science (see chart, above). For example, Masliah placed first for papers that use the terms “synuclein” and “synapse.”

His most influential work includes fundamental studies of synaptic damage in mice genetically engineered to mimic various neurodegenerative conditions. “People are very dependent on all of these descriptions,” says Perry, who also reviewed the dossier on Masliah’s research for Science. Many are among the 132 questioned papers, which have racked up more than 18,000 citations, often by leading scholars. “Now I think that work was probably fabricated, in part,” Perry adds, calling the influence of the questioned papers “very problematic.”

BEGINNING IN 2023, forensic image sleuths began to flag a few papers in which Masliah played a central role, posting to PubPeer, an online forum where research publications are discussed and allegations of misconduct often raised. In a few cases, Masliah or a co-author replied or made corrections. Soon after, Science spotted the posts, and because of Masliah’s position and standing decided to take a deeper look.

Schrag, Columbia University neurobiologist Mu Yang, and independent forensic image analyst Kevin Patrick agreed to examine a wider swath of Masliah’s output. (Patrick, a nonscientist who uses the moniker “Cheshire” on social media, had pseudonymously submitted several PubPeer posts on Masliah papers.) In 2023, after a similar request from Science, the same group had assessed work by University of Southern California (USC) Alzheimer’s and stroke expert Berislav Zlokovic. Their dossier of possible misconduct and a subsequent Science report prompted university and NIH investigations, which are apparently ongoing, and led NIH to pause a late-stage clinical trial of a stroke drug based in part on apparently manipulated studies.

For the new dossier, Schrag provided examples, technical context, and expertise on how the findings might affect the promise of prasinezumab and other drugs. Yang took the lead role in identifying and examining questionable images. She used Image- twin, a software program, to assist her own personal scrutiny. (The software, for example, initially spotted the reused mitochondrion image.) Schrag and Yang worked independently of their employers.

Microbiologist and research integrity expert Elisabeth Bik, who also worked on the Zlokovic dossier, contributed other Masliah examples and reviewed and concurred with almost all of the findings. All of the dossier authors worked as volunteers, poring over papers and images in their spare time. The group says it will post many of the examples from the Masliah dossier on PubPeer for others to review; Schrag provided the dossier to NIH, as did Science in the course of producing this story. (NIH’s statement says it had initiated its own investigation much earlier, in May 2023, after receiving allegations from the HHS Office of Research Integrity [ORI].)

In Yang’s analysis of multiple Masliah-authored papers, duplicated sections in some Western blots that had been “seamlessly blended” quickly floated into view, she says. “It tells me someone put a lot of thought and effort into the image … and usually indicates something is very wrong.”

Yang began to see patterns in the apparent image doctoring, which also included images that had been duplicated or seemingly altered by “cloning” portions of them. “I started feeling like a curator or art historian—when you look at a piece of art without the label, you know the artist by the style. Like a painting from Picasso’s blue period,” she adds, “it’s a signature style that I saw in many, many papers—the way they lay out the figures, even the color contrast.”

After finding hundreds of questionable images, the group had more than enough strong signs of misconduct and stopped looking, Yang says. But she suspects similar problems would emerge from a close examination of the hundreds of other Masliah papers.

Making a drug look better?

National Institute on Aging neuroscience chief Eliezer Masliah was senior author of a 2015 study of the Alzheimer’s disease treatment Cerebrolysin in BMC Neuroscience. Brain-tissue images from normal mice and mice engineered to overexpress a mutant form of the tau protein might have been doctored to suggest the drug reduces damage from the tau.

Overlapping copies

In the paper, normal (non-tg) mice show no tau damage. The mutant mice (3RTau) show tau damage unless treated with Cerebrolysin. But a merged image of the younger, normal mouse and the older, treated mutant appear unnaturally similar. Yellow sections are identical.

A series of clones

Dissimilar (red or green) areas within the merged image seem to be caused by efforts to obscure the duplication. Small “cloned” areas within each image are indicated by same-color boxes. The journal’s publisher said it would review the concerns.

YANG AND THE OTHER authors say the ongoing human trials of prasinezumab add to the urgency of their findings. According to Prothena, the drug blocks the spread of toxic alpha-synuclein and might slow the progression of Parkinson’s movement disorders and dementia. Prasinezumab’s documented side effects have not been dangerous. But if it is based on suspect scientific foundations and, as the first clinical results suggest, ineffective, further clinical testing could raise false hopes and divert patients from trials of other experimental drugs.

The concept for prasinezumab emerged from Masliah’s ties to the late Dale Schenk, a UCSD-trained neuroscientist whose research helped pioneer the idea of treating Alzheimer’s and Parkinson’s with vaccines designed to block the buildup of harmful amyloid and synuclein. Masliah, Schenk, and others proposed that immunizing people with benign parts of each protein could spur the immune system to produce antibodies that might block the full, toxic form. Infusing labmade antibodies might have the same effect. Either approach, they hypothesized, could offer a “disease modifying” attack on a condition’s root cause, rather than merely alleviating symptoms.

In a 2016 post on Alzforum, Masliah recalled an early discussion with Schenk on the idea. “Dale and I sat at a coffee shop (his favorite place) next to the Pacific Ocean and drew, on a napkin, the concept of how a potential synuclein vaccine might work,” he said. “People strongly doubted the potential use of a vaccine approach in Alzheimer’s and even more so in Parkinson’s. Dale was one of the few who listened and believed in the idea.”

To pursue that vision Schenk co-founded and served as chief executive of Prothena, spun off in 2012 from the former biopharma company Elan. Masliah worked extensively with Schenk until his death from pancreatic cancer at age 59 in 2016. Four of their joint studies, published between 2005 and 2017, proved foundational for prasinezumab, according to Prothena’s promotional material. Schenk was senior author on two of the papers, Masliah on two. All four used apparently doctored images, according to the dossier, as did other Masliah papers cited in clinical trial reports as important to prasinezumab’s development. Some of the papers suggested Parkinson’s symptoms could be generated in mice engineered to produce alpha-synuclein, and that those symptoms could be reduced by injecting antibodies akin to prasinezumab into the animals.

Greenamyre, a Parkinson’s specialist, says the papers showed an “astonishing level” of apparent image manipulation. But he notes that the image anomalies and the drug’s lack of success so far don’t necessarily mean “that synuclein is a bad target or that targeting it with antibodies is never going to work.” The clinical trial team testing the antibody reported earlier this year in Nature Medicine that a small subgroup of its patients showed hints that prasinezumab slows the worsening of movement symptoms—although the group acknowledged that the finding emerged in a “posthoc analysis,” a secondary review unrelated to the trial’s hypothesis.

Manipulations in key experiment?

Five images in a 2005 paper in Neuron from Masliah and Prothena founder Dale Schenk appear to have been doctored in ways that could influence paper's findings. It is among several papers cited as key to the experimental drug prasinezumab that show apparent falsifications.

Still, “The discovery that key papers supporting this approach contained manipulated figures certainly muddies the waters,” Greenamyre says. He’s now hoping independent studies will determine whether “the rationale for clinical development remains on firm ground—or if it is now a little shaky.”

“We do not interpret these claims as specifically relevant to the current prasinezumab clinical program,” Prothena told Science in a brief statement responding to questions about the image anomalies related to the drug.

Swiss pharma giant Hoffmann-La Roche, which partnered with Prothena to develop prasinezumab in 2013, also supplied a statement in response to Science’s questions, saying it would continue clinical development of the drug. “The evidence supporting targeting alpha-synuclein aggregates as a mechanism of action in [Parkinson’s] is based on a wide range of sources,” it stated. In the interest of scientific integrity, Roche added, “We are working to further understand the details of this matter.”

Roche has agreed to pay Prothena up to $620 million if its drug candidate passes a series of performance goals. So far, Roche has paid $135 million.

Schenk and Masliah shared inventor credit in patents in the U.S. and Europe related to synuclein, amyloids, and related science, and they and their co-inventors assigned the rights to Prothena, UCSD, or both. Numerous other Prothena patents refer to suspect work cited in the dossier. Prothena and NIH did not respond to questions about whether Masliah has received or was promised royalties.

The dossier also questions some of Masliah’s earliest work on alpha-synuclein, raising further doubts about the foundations of Prothena’s drug. A seminal 2000 Masliah article in Science, for example, suggested alpha-synuclein might kill certain brain cells and speed the development of brain deposits called Lewy bodies that are hallmarks of Parkinson’s and are often seen in Alzheimer’s patients. But the paper contains an apparently doctored image and another image the dossier authors deemed questionable.

Other researchers have yet to validate aspects of that study, according to Ayton and neurologist Michael Okun of the University of Florida.

“A single nonreplicable finding is in itself not worrisome,” Okun says. But it raises greater concern in light of “convincing evidence of spliced and cloned images which appeared frequently in the decades following.” He calls it “deeply troubling” that FDA greenlighted human trials of prasinezumab based largely on suspect papers from Masliah’s lab.

People will, of course, be shocked, as I was. ... I was falling from a chair, basically.

Christian Haass

Ludwig Maximilians University Munich

FDA declined to comment on the prasinezumab findings challenged within the dossier. Holden Thorp, editor-in-chief of the Science family of journals, says the journal will “contact the authors [of the 2000 paper] to hear their response to these concerns. If any adjustments are required, we will certainly make them.” (Science’s News department is editorially independent of the journal.)

The new phase 2 trial of prasinezumab is examining whether it might slow the progression of certain movement difficulties caused by Parkinson’s, as the posthoc analysis suggested it might. Roche and Prothena expect to announce preliminary results later this year. The companies would likely decide in 2025 or 2026 on whether to move on to phase 3 trials—larger efficacy experiments needed for possible FDA approval.

The findings in the dossier cast a shadow on the other drug development efforts that rely on Masiah’s challenged work. And they raise questions about the roles and responsibilities of the many prominent scientists as well as more junior researchers who collaborated on some of his suspect experiments.

UCSD neuroscientist Edward Rockenstein, who worked under Masliah for years, co-authored 91 papers that contain questioned images, including 11 as first author. He died in 2022 at age 57. And neuroscientist Robert Rissman worked on 16 of the papers highlighted in the dossier, seven as senior author. He managed biomarkers and brain tissue samples for UCSD’s Alzheimer’s Disease Research Center prior to moving recently to USC, where he occupies a similar role and manages programs that try to move basic research into treatments for patients. Rissman did not reply to requests for comment. USC says it will conduct a confidential review of Rissman’s involvement with Masliah’s work.  

Haass questions whether Masliah’s closest collaborators could have remained unaware of the steady stream of apparent image manipulation, even if they were not personally culpable. “I mean, come on,” he says. “They must know.”

Other neuroscientists who spoke to Science urged caution in placing blame. “We should be careful … not to rush to judgment on the generation of researchers who may have been innocent members of this laboratory over the span of 20-plus years,” Okun says. “It is entirely possible that many were unaware of improprieties.”

In its statement today, NIH provided few details about the agency’s own investigation into Masliah’s work, including whether it had examined more than two of his publications. The agency says it has notified ORI of its findings and that the NIA deputy director, Amy Kelley, is also now acting head of the neuroscience division.

Given the NIH misconduct determination and the questions raised by the dossier about more than 100 other papers, many scientists—and perhaps congressional appropriators and the public—might question NIH’s vetting process for key roles and how Masliah retained stewardship of NIA’s billions of neuroscience dollars for so long. “For so important a job, you want somebody who is beyond reproach. You want somebody to be an exemplar of what you aspire to be,” Greenamyre says.

By the time NIA hired Masliah in 2016, image manipulation in scientific papers had already become a general concern. Prominent researchers increasingly faced accusations of image manipulation, plagiarism, or other misconduct—which often proved credible. But a former NIA official who would only speak if granted anonymity says he assumes the agency did not assess Masliah’s work for possible misconduct or data doctoring before he was hired.

Indeed, NIH told Science it does not routinely conduct such reviews, because of the difficulty of the process. “There is no evidence that such proactive screening would improve, or is necessary to improve, the research integrity environment at NIH,” the agency added.

Gandy disagrees. “It has to be part of the process now,” he says.

Greenamyre notes a concern about the episode also voiced by Haass and others who viewed the dossier: “I worry about it giving science a further black eye, just as the public’s confidence in science and scientists is sinking to new depths.” But, Greenamyre says, “In the interest of transparency and scientific integrity, this sad story has to come out.”

Questionable papers underpin other drugs

By Charles Piller

The possibility that neuroscientist Eliezer Masliah doctored images in scientific writings for decades is likely to provoke anxiety among multiple drug companies. The concerns documented by whistleblowers most directly challenge an experimental Parkinson’s therapy developed by Prothena (see main story). But 238 active patents concerning neurological conditions also cite suspect work noted in the dossier, according to data from Dimensions Analytics. And the corporate holders of those patents include dozens of firms at work on treatments.

The Austria-based biopharma company Ever Pharma relied heavily on Masliah’s questioned work in developing Cerebrolysin, a mixture of peptides—short chains of amino acids—derived from pig brains. Eight studies conducted at Masliah’s former lab at the University of California San Diego, funded in part by Ever Pharma, indicated the mixture suppresses brain inflammation, promotes growth of new brain cells, and has other benefits that could help dementia patients.

Small clinical trials of Cerebrolysin have suggested modest cognitive benefits in Alzheimer’s disease and vascular dementia, and Ever Pharma now distributes the drug in dozens of nations to treat dementia and stroke. But no large trials have demonstrated it helps dementia patients, and the Food and Drug Administration has not approved Cerebrolysin for use in the United States. And the eight lab studies used suspect images, according to the dossier.

For example, an article by Masliah and colleagues, in BMC Neuroscience in 2014, described the purported benefits of Cerebrolysin for symptoms of neurodegeneration in mice, including reducing mitochondrial damage. Another, published in Neurotoxicity Research in 2016, concerned mice infected with HIV. It republished what appears to be the same image of a mitochondrion.

A spokesperson for Springer Nature, publisher of Neurotoxicity Research, says the concerns will be examined, and responded to if warranted. Stefan Winter, who heads R&D for Ever Pharma’s neurological division, said in a written statement to Science that none of the challenged work in the dossier “played a crucial role in the clinical development of Cerebrolysin.” But, he added, “We take [the allegations] seriously. We will therefore review Prof. Masliah’s work based on the information you provided and refrain from using data from the mentioned publications until this matter is clarified.”

Another company, Neuropore Therapies, cites seven other papers in the Masliah dossier—all with apparently doctored images—as important to the company’s potential drugs for Parkinson’s. Masliah co-founded Neuropore in 2008 but no longer has any apparent affiliation. The most prominent drug candidate his work helped develop, minzasolmin, is in early clinical trials and targets the protein alpha-synuclein for Parkinson’s.

Masliah also provided imaging services for a 2023 paper in NPJ Parkinson’s Disease. The images, which purportedly show enhanced benefits in mice from minzasolmin, appear to be altered, according to the dossier. The concerns will be examined and responded to if warranted, says the journal’s publisher, Springer Nature. “We stand by our data related to clinical development programs,” said Mark Yung, executive chairman of Neuropore, in a brief written reply to detailed questions.

Minzasolmin has Big Pharma backing. In 2015, Neuropore licensed rights to develop and commercialize it and other molecules to the Brussels-based pharma company UCB for $63 million, plus possible future payments. In turn, the Swiss pharma titan Novartis paid UCB $150 million of a possible $1.5 billion for codevelopment rights for minzasolmin and another experimental drug.

“UCB will investigate the preclinical publication on minzasolmin” described in the Masliah dossier and will respond should “evidence of impropriety emerge,” said company spokesperson Laurent Schots in a written statement. But UCB knows of no “facts or circumstances that raise concerns on the quality, validity, and safety of the ongoing clinical development program for minzasolmin,” which is supported by evidence beyond the suspect Masliah work, Schots added.

Preliminary results for the drug’s efficacy from a clinical trial of 496 people in the U.S., Canada, and Europe could be announced later this year.

[ainews]

A recent and alarming shortage of neuropathologists has made it increasingly difficult for neurosurgeons to obtain brain pathology reports needed to diagnose and treat patients. This has placed greater importance on parchment, which is still used in labs as an efficient method of determining the cause of neurodegenerative diseases.

Parchment, or "brain paper," is made from acid-free, archival paper, that has been treated with a special sealant. The sealant helps preserve delicate brain tissue, allowing physicians to view and monitor the deterioration process of a patient's brain. Neuropathologists rely on parchment to provide an accurate diagnosis, as this medium works to ensure the disease's effects are not altered or disturbed.

In recent years, the demand for neuropathologists has grown exponentially, leading to a shortage in the growing field. Neuropathologists often burn out quickly due to the significant amount of time and responsibility involved in their job. This has caused the shortages in neuropathologists, as fewer and fewer people are willing to do the job and the turnover rate has hit an all-time high.

With the high demand for neuropathologists, parchment and other specialized brain paper products have become increasingly rare and expensive. This has created an added challenge for medical institutions, who must now balance budget constraints with the need to obtain the necessary material to conduct the examination of brain tissue. As a result, many medical labs have begun to utilize alternative methods of examining brain tissue, such as digital imaging and artificial intelligence, in place of parchment.

Parchment is still widely regarded as the gold standard for examining brain tissue because it offers much more precise imagery of the brain tissue than the alternatives. Without the use of parchment, neuropathologists are unable to properly survey the tissue and make an accurate diagnosis about a diagnosis. This is why neuropathologists are so passionate about parchment and will continue to look for ways to ensure its longevity.

[ryanthedemiboy]

Apparently covid has been shown to reduce thickness of gray matter in the frontal and temporal lobes, which would likely mimic the symptoms of frontotemporal dementia.

Symptoms of which include reduced empathy, among many other things.

Neuropathologist (MD, PhD) brought this to my attention on twitter. Thread: https://twitter.com/JamesThrot/status/1768304255109079367?t=CE6p93T6dL_8C_uSOVY4ow&s=19

Anywho, wear a mask.

giving even a single shit abt covid will actually make u feel fucking crazy sometimes lol