MEDICINE AND HEALTH

Alzheimer’s disease drugs neutralize amyloid small mers


Alzheimer’s, or Alzheimer’s disease (AD), affects more than 50 million people worldwide. Now, American scientists have described a special type of amyloid structure β, small aggregates of amyloid that float in brain tissue fluid, reach many areas of the brain, and disrupt local neuronal function. The study shows that a newly approved AD therapy can neutralize these small diffusive aggregates. Related research was recently published in Neurons.

Scientists have discovered an abnormal buildup of amyloid, a naturally occurring substance in the brains of AD patients, that disrupts neurotransmission. There is currently no cure for this disease. But in recent years, scientists have developed new treatments that can reduce AD symptoms, such as memory loss.

“Our study found a drug that can really treat AD, slowing cognitive decline in patients.” The paper’s corresponding author, Dennis Selkoe of Brigham and Women’s Hospital in the United States, said.

In January, the U.S. Food and Drug Administration (FDA) approved lecanemab, a drug used to treat AD. In a phase III clinical trial, lecanemab slowed cognitive decline in patients with early-stage AD. Scientists speculate that the drug’s positive effects may have something to do with its ability to bind and neutralize soluble amyloid aggregates β. Also known as fibrils or oligomers, these aggregates are tiny, free-floating amyloid clumps. These small clumps can form in the brain and then further aggregate into large amyloid plaques. Small aggregates can also break and spread.

“But no one can really define structurally what is a ‘fibril’ or ‘oligomer’ of lecanemab’s action.” Lead author Andrew Stern, a neuroscientist at Brigham and Women’s Hospital, said, “Our work is to isolate this structure from the human brain. This is important because patients and drug developers alike want to know exactly what lecanemab combines with. ”

Stern, Selkoe and colleagues succeeded in isolating free-floating β amyloid aggregates by immersing postmortem brain tissue samples from typical AD patients in saline solution and then rotating them at high speed. These tiny aggregates of amyloid can enter important brain structures such as the hippocampus, which plays an important role in memory. Working with colleagues at the Laboratory of Molecular Biology in Cambridge, UK, they determined the atomic structure of these tiny aggregates.

“If you don’t know your enemies, it’s hard to defeat them.” Zelkoe said, “It’s a very good coincidence that the work we do is done when lecanemab is available. The study analyzes the identity of the ‘bad guys’ and how the ‘new weapons’ defeat the ‘bad guys’. ”

Next, the team plans to observe how these tiny β amyloid aggregates travel in the brains of living animals and study how the immune system responds to these toxic substances. Recent studies have shown that the brain’s immune system’s response to amyloid is a key part of AD.

Stern said: “If we can figure out exactly how these tiny, diffusible fibrils exert toxicity, the next AD drug may be even better.” (Source: China Science News, Jinnan)

Image source: Pixabay

Related paper information:http://doi.org/10.1016/j.neuron.2023.04.007



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