News analysis: Why does the United States heavy Alzheimer's Patient Fate cause controversy?

Alzheimer's disease, known as the "rubber rubbing in the mind", is a neurodegenerative disease that is unclear and cannot be cured. The US "Science" magazine recently released a survey report that an important foundation research paper in the field of Alzheimer's disease 16 years ago was suspected of fraud and threatened the mainstream theory "β amyloid protein deposition (Aβ)". And the impact of new drug research and development.

Suspected fraud

Over the years, the research and development of Alzheimer's drugs is mainly based on the most recognized "hypothesis" -t beta starch -like protein deposition. The abnormal deposition of the brain β amyloid -like protein may cause a series of reactions such as TAU protein excessive phosphorylation, neurotransmitter disorders, and oxidation stress, which causes neurons to be damaged and then dementia. Prevent β amyloidin deposition is considered to be the most reliable treatment strategy. But for decades, hundreds of clinical trials with β starch protein as targeted therapies ended in failure, and more and more scientific researchers began to doubt the hypotheum.

Until 2006, the graduate student of the University of Minnesota, Silwan Leine, published a paper as the first author in the British "Nature" magazine, which directly proves that the subtype Aβ*56 of the β amyloid protein has neurotoxicity, which will lead Mouse dementia, which is equivalent to injecting "strong heart needle" into the beta starch -like protein. At that time, "Nature" commented that Aβ*56 was the "number suspect" of Alzheimer's disease.

This is the paper that was suspected of fraud. It was found that the suspicion was Matthew Schraigg, a neurologist at the University of Vanderbelt. In 2021, Schrag accidentally found that there were problems with many papers in Laine. Most papers were related to Aβ*56, including papers published in Nature.

Schrag will find it to "Science", and then "Science" conducts a six -month investigation, which strongly supports Sratrag's doubt. Independent image analysts and some top Alzheimer's disease researchers reviewed these images at the request of Science and agreed that there were dozens of pictures in the Laine thesis that might have problems.

However, whether the dissertation confirms fraud at present, it has not been concluded. "Science" said that relevant researchers need to provide complete, unpublished images and original data to distinguish. The University of Minnesota is also reviewing the dispute points of Lyne research, which may take several years.

Controversy

"Science" said that Schrag's discovery may threaten the main theories in the field of Alzheimer's disease. Statistics show that the number of citations in the paper has exceeded 2300 times. According to reports, the National Institute of Health has spent about $ 1.6 billion on β amyloid -related projects this year, accounting for about half of its total funds for Alzheimer's disease research.

However, some neurosciences interviewed by the reporter said that the questioned papers could not shake the current mainstream position of β amyloid protein hypotheses. Li Yanfeng, chief physician of the Department of Neurology, Beijing Union Hospital, told reporters that even if the thesis confirmed fraud, the impact on related research was limited. At present, the mainstream conclusion of the academic circles for Alzheimer's pathogenesis is still β amyloid protein hypothesis. Β amyloid protein deposition is still an important pathological symbol of Alzheimer's disease and the cause of triggering neurotherapy.

Wang Chengzheng, a professor of the Department of Science and Technology and Science and Technology of the University of Science and Technology of China, said in an interview with reporters: "From the perspective of scientific history, many scientific discoveries start from hypothesis. Potations are constantly proposed, proven or falsified. Scientific progress is essential for natural processes. The transformation of the direction is also very slow, especially the hypothesis of some 'open -minded holes', which will not be easily denied because there are problems with one or two experiments. "

In fact, the controversy about β amyloid -like protein hypotheses has always existed. Dr. Qiu Zhihai, the Institute of Intelligence Science and Technology of Guangdong Province, told reporters that it is generally believed that there are extracellular starch -like plaques formed, and then neuroplastin death is recently killed. Blocks appear, and follow -up related research is worth looking forward to.

R & D black hole

Alzheimer's Disease has always been a "black hole" for pharmaceutical companies. R & D mainly focuses on β amyloid -like protein and TAU protein deposition. However, in recent years, the clinical trials that target these two targets have rarely succeeded, leading to the "monopoly" β amyloid -like protein hypothesis in the field in this field has faced more and more doubts.

A report from the American Pharmaceutical Research Institute and the Pharmaceutical Manufacturer Association showed that from 1998 to 2017, a total of 146 Alzheimer's clinical trials failed. Qiu Zhihai said that many drugs have controversial research and development, mainly due to unclear efficacy. Possible reasons include: first, insufficient understanding of Alzheimer's pathogenic, and the target is not right. Second, there is a lack of good animal models and cannot be clinically clinically. Past -drug effects were fully tested.

However, experts believe that the new targets and new hopes are constantly appearing in the development of Alzheimer's new drugs in the dispute.

The report released by Alzheimer's Disease Discovery Foundation shows that the existing R & D pipeline of Alzheimer's disease not only focuses on β amyloid protein and TAU protein, but also targets various innovative targets. At present, there are 118 clinical development phase aimed at changing the process of Alzheimer's disease. As many as 77%of therapy involves multiple areas related to aging and neurodegenerative diseases, including neuropapture, inflammation, mitochondrial and Metabolic functions, synapses and neurotransmitters, genetic and epigenetics, etc.

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