In a report published in Neuron, a research team reveals the structure of the therapeutic target of lecanemab, a drug approved by the US Food and Drug Administration in January 2023 for the treatment of Alzheimer’s disease.

While the drug had been thought to selectively target soluble amyloid-beta protofibrils, the structure of these targets in the human brain had not been known. In their study, researchers characterized amyloid-beta fibrils from the human brain and found unexpected results, which help clarify how lecanemab has its protective effects with implications for future drug design.

The authors show that the diffusible Aβ fibrils have the same atomic structure as amyloid plaque fibrils and lecanemab binds to and protects against the synaptotoxicity of diffusible fibrils.

“For the first time, we describe the structure of a special type of amyloid beta plaque protein associated with Alzheimer’s disease progression, revealing the identity of the enemy,” said the senior author. “These findings are extremely timely as we make key strides in developing treatments that can reduce cognitive decline.”

“Defining how these tiny, diffusible fibrils exert toxicity will not only inform our understanding of Alzheimer’s disease but also help us design better drugs against it,” said another author.

https://www.cell.com/neuron/fulltext/S0896-6273(23)00269-6

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fabundant-ab-fibrils-in&filter=22