For the first time, researchers described the structure of a special type of amyloid beta plaque protein associated with Alzheimer’s disease (AD) progression. Published May 10 in the journal Neuron, this research also provided evidence that a newly approved AD treatment could neutralize these small, diffusible aggregates.
In January, the U.S. Food and Drug Administration approved lecanemab, an antibody therapy for treating AD. In a phase III clinical trial, lecanemab slowed cognitive decline in patients with early AD.
Scientists suspect the drug’s positive effect may be associated with its ability to bind and neutralize soluble amyloid beta protein aggregates, also known as protofibrils or oligomers, which are tiny, freely floating clumps of the amyloid beta protein.
Stern, Selkoe, and their team successfully isolated the free-floating amyloid beta aggregates by soaking postmortem brain tissues from typical AD patients in saline solutions, which were then spun at high speed.
These tiny aggregates of amyloid beta protein access important brain structures such as the hippocampus, which plays a major role in memory.
Next, the team plans to observe how these tiny amyloid beta aggregates travel through living animal brains and study how the immune system responds to these toxic substances. Recent research has shown that the brain’s immune system reaction to amyloid beta is a key component of AD.
“If we can figure out exactly how these tiny, diffusible fibrils exert toxicity, then maybe the next AD drugs can be better,” Stern says.
Andrew M. Stern, Yang Yang, Shanxue Jin, Keitaro Yamashita, Angela L. Meunier, Wen Liu, Yuqi Cai, Maria Ericsson, Lei Liu, Michel Goedert, Sjors H.W. Scheres, Dennis J. Selkoe. Abundant Aβ fibrils in ultracentrifugal supernatants of aqueous extracts from Alzheimer’s disease brains. Neuron, 2023; DOI: 10.1016/j.neuron.2023.04.007
Cell Press. (2023, May 10). FDA-approved Alzheimer’s drug lecanemab could prevent free-floating amyloid beta fibrils from damaging the brain. ScienceDaily. Retrieved May 16, 2023 from www.sciencedaily.com/releases/2023/05/230510120523.htm
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