A drug against Alzheimer's manages to reduce memory loss for the first time in history

Historic day for Alzheimer's patients. For the first time, a drug approved by the US Government's Food and Drug Administration has been shown to be able to “slow down cognitive decline and memory loss,” according to a team of scientists from Brigham and Women's Hospital in Boston ( USA) in the journal Neuron.

Thus, the results of the experimental study have pioneeringly described the structure of a special type of amyloid beta plaque protein, essential for the transmission of information between neurons, and associated with the progression of Alzheimer's disease.. In this way, scientists have shown that small aggregates of this protein float through brain tissue fluid, reaching many regions of the brain and altering the functioning of local neurons.

Research has succeeded in isolating small amyloid aggregates from the brains of postmortem Alzheimer's patients. This achievement has made it possible to study the structure of these “lumps”, which exist outside the plates and are considered highly toxic, as well as to verify their effect on synapses.. The research also provides evidence that the lecanemab treatment, an antibody therapy that could neutralize these small diffusible aggregates, is capable of binding to them and helping to neutralize their action.

Alzheimer's, one of the causes of dementia, affects more than 50 million people worldwide.. Previous research has found that AD patients have an abnormal buildup of a naturally occurring substance—amyloid beta protein—in the brain that can alter neurotransmission.. Currently, the disease has no cure.. But in recent years, scientists have developed new treatments that can reduce AD symptoms, such as memory loss.

“For the first time in human history”

“The article is very timely because, for the first time in human history, we have an agent capable of treating Alzheimer's patients in a way that slows their cognitive decline,” said Dennis Selkoe, author of the Brigham article. and Women's Hospital in Boston, who continues: “We had never been able to say those words until the last few months”. And, in a phase III clinical trial, lecanemab slowed cognitive decline in patients with incipient AD.

The scientists suspect that the drug's positive effect may be linked to its ability to bind to and neutralize soluble amyloid beta protein aggregates, also known as protofibrils or oligomers, which are small, free-floating clumps of amyloid beta protein.. These small clumps can form in the brain before further aggregating into large amyloid plaques.. Small aggregates can also detach and diffuse from already existing amyloid plaques.

“But no one has been able to define with structural rigor what a 'protofibril' or 'oligomer' is that lecanemab binds to,” said Andrew Stern, a neurologist at Brigham and Women's Hospital and first author of the study.. “Our work identifies this structure after isolating it from the human brain. This is important because patients and drug manufacturers will want to know exactly what lecanemab binds to.. Could you reveal something special about how it works?” he wonders.

This is how Stern, Selkoe and their team were able to isolate the floating beta-amyloid aggregates by immersing postmortem brain tissues from typical AD patients in saline solutions, which were then centrifuged at high speed.. These tiny amyloid beta protein aggregates gain access to important brain structures such as the hippocampus, which plays a key role in memory.. In collaboration with colleagues at the Cambridge Molecular Biology Laboratory, UK, they determined the atomic structure of these tiny aggregates, right down to the individual atom.

“If you don't know your enemies, it's hard to beat them,” Selkoe exemplifies. “It was a very nice coincidence that all this work we were doing coincided with the time that lecanemab became widely known and available.. This investigation brings together the identity of the bad guy and something that can neutralize him.”

Next, the team plans to observe how these tiny amyloid beta aggregates travel through the brains of living animals and to study how the immune system responds to these toxic substances.. Recent research has shown that the brain's immune system's reaction to amyloid beta is a key component of AD.. “If we can figure out exactly how these tiny diffusible fibrils exert their toxicity, perhaps the next AD drugs may be better,” says Stern.