In patients with Alzheimer’s disease, there are abnormal accumulations of amyloid plaques in the brain, which naturally occur in the body. These amyloid plaques are an accumulation of a protein called p-tau and they disrupt cell function. Research is being done to better understand how and when these amyloid plaques form. Now, researchers believe that they have identified a compound that can reduce the number of amyloid plaques in the brain and lessen brain inflammation.
Liviu Mirica, a chemistry professor at the University of Illinois at Urbana-Champaign who led the research notes, “It's possible that the amyloid plaques somehow trigger the aggregation of the p-tau proteins in the extracellular environment, and this process then spurs the spread and formation of p-tau inside the neurons, where it starts to clump together."
This clumping leads to what is called “neurofibrillary tangles” which disrupt cell function and ultimately kill the cell. Scientists still do not understand everything at work with Alzheimer’s disease. Some studies have tried to dissolve or disrupt the amyloid plaques, which contain a protein fragment called beta-amyloid peptide. According to Mirica, “Everybody was trying to attack the amyloid plaques to dissolve them, but we've learned that Alzheimer's is a bit more complicated than we thought. Studies have found strong evidence that these soluble peptides are the most neurotoxic species and are causing memory loss and neuron cell death. Plaque formation might be an attempt by the brain to neutralize the threat.”
Copper and iron are also part of the pathology of Alzheimer’s. These metal ions form associations with the beta-amyloid peptide and contribute to oxidative stress and brain inflammation. "To address these different pathological aspects of Alzheimer's disease, we developed a compound known as L1 that interacts with different regions of the beta-amyloid peptide, as well as with metal ions," Mirica said.
Mirica continued, "When tested in mice genetically predisposed to develop Alzheimer's-like pathologies, our compound could cross the blood-brain barrier, reduce neuroinflammation and decrease the levels of amyloid plaques and of p-tau aggregates associated with these plaques."
This research, which is published in the journal, ACS Chemical Neuroscience, provides insight for drug development. Drugs that interact with amyloid-beta protein fragments could help improve the lives of Alzheimer’s patients.