Possible Fabrications Found in Alzheimer’s Research

A Tennessee professor has found “fabrications” in data from a pivotal Alzheimer’s study from 2006.

Charles Piller, an investigative journalist for Science magazine, discussed a Tennessee junior professor’s troubling findings in one of the most cited Alzheimer’s disease studies in this century.

Matthew Schrag, a 37-year-old physician and neuroscientist from Vanderbilt University, expressed doubts about the validity of a research paper published in 2006 on the primary role of amyloid-beta (Aβ) plaques in causing Alzheimer’s disease.

In August 2021, Schrag received a call from his colleague who wanted to connect him with an unnamed attorney investigating Simufilam, an anti-Aβ plaque experimental drug for Alzheimer’s disease.

Cassava Sciences, Simufilam’s developer, claimed that the drug improved cognition by partly repairing a protein that can block sticky brain deposits of the protein amyloid beta (Aβ), a hallmark of Alzheimer’s.

Schrag has once publicly criticized the controversial FDA approval of the anti-Aβ drug Aduhelm, as his research also contradicted some of Cassava’s claims and worked with the attorney to probe into published images about Simufilam and its science.

However, Schrag discovered findings threatening the 2006 paper on the primary role of amyloid-beta (Aβ) plaques in causing Alzheimer’s disease, which served as the scientific foundation for developing Simufilam.

Schrag discovered possibly tampered images in papers from the University of Minnesota, Twin Cities, neuroscientist Sylvain Lesné, including a 2006 paper in Nature co-authored with Karen Ashe and others.

“So much in our field is not reproducible, so it’s a huge advantage to understand when data streams might not be reliable. Some of that’s going to happen reproducing data on the bench. But if it can happen in simpler, faster ways, such as image analysis, it should,” Schrag said.

Science magazine conducted a 6-month investigation into Schrag’s discoveries, further confirming his suspicions and raising questions about Lesné’s research.

A leading independent image analyst and several top Alzheimer’s researchers, including George Perry of the University of Texas, San Antonio, and John Forsyth of the University of California, San Francisco (UCSF), reviewed most of Schrag’s findings at Science’s request, concurring with his overall conclusions and casting doubts in hundreds of images, including more than 70 in Lesné’s papers.

However, Schrag’s discovery has massive financial implications.

“The immediate, obvious damage is wasted NIH funding and wasted thinking in the field because people are using these results as a starting point for their own experiments,” said Nobel laureate and Alzheimer’s expert Thomas Südhof.

Further research is essential to understand the role that Aβ plaques play in Alzheimer’s disease if any.

“You can cheat to get a paper. You can cheat to get a degree. You can cheat to get a grant. You can’t cheat to cure a disease. Biology doesn’t care,” Schrag said.

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