Diagnosis of Alzheimer’s disease The world of foreign exploration over the past two years has been like riding a mountain road without a belt. In 2021, the US Food and Drug Administration took a surprising step to influence its advisory committee to approve the sale of Aduhelm, the first drug for Alzheimer’s in almost two decades. The drug is designed to work by removing the build-up of amyloid beta, a protein that has been linked to the disease, from the patient’s brain. In clinical trials, the drug he said Get rid of amyloid – but it didn’t make a better diagnosis, so the committee recommended against it.
But the FDA determined that the amyloid approval was sufficient, and granted Aduhelm an expedited approval. The decision was highly controversial – it triggered an internal investigation by Congress, and three members of the advisory committee resigned.
Suddenly, journalists across the country were rushing to destroy the “amyloid hypothesis” to their readers, to explain why the FDA would approve a drug without evidence that it reduces symptoms—and why the decision caused so much controversy. The story went like this: For years, many scientists have believed that Alzheimer’s disease is caused by amyloid beta plaques, misfolded amyloid beta proteins, possibly because the plaques are toxic to neurons. Opponents said that the amyloid camp has been working for a long time in the field, forcing other ideas – despite the repeated failure of amyloid drugs, which, according to the amyloid hypothesis, should work. Then in 2022, Science described the charges against an amyloid researcher who was accused of gross and systematic dishonesty, and proved that the amyloid hypothesis was a dubious idea promoted by fraudsters.
This September, the journey took another turn with the release of preliminary results from a Phase 3 trial of lecanemab. Like Aduhelm, lecanemab is an antibody that targets amyloid beta, and was developed by the same company. But this time, medicine he said Slow cognitive decline in a clinical trial of nearly 2,000 people with early Alzheimer’s disease. In general, everyone’s cognition worsened during the trial, but those who received the drug experienced a significant decrease compared to those who received a placebo. The difference was small: After 18 months, patients on lecanemab only had a gradual decline in the level of cognitive function that increased by half.
After a lot of shaking and complaining about the idea of amyloid, this new drug seems to have confirmed it—lecanemab removed amyloid beta from people’s brains, and their disease decreased. In the research world, however, the issue is not so black and white. After years of failed treatments, Alzheimer’s scientists are happy that something might work, if modestly. But the results of the trials are complicated—perhaps because the concept of amyloid itself is not as straightforward as it might seem.
“In general, people would say amyloid is important. I don’t think anyone is saying amyloid no important, “said Eleanor Drummond, Bluesand senior researcher at the University of Sydney. The question, she says, is “whether it’s the be-all and end-all”—enough to justify drug approval with little evidence of benefit, and enough to control Alzheimer’s drug research.
