By Yehudis Kundin
Alzheimer’s disease is the most common form of dementia, characterized by a gradual loss of cognitive functions, such as reasoning, judgement, thinking and memory. These symptoms greatly interfere with patients’ ability to perform daily tasks such as eating, drinking and dressing. Current estimates suggest that 7.2 million Americans aged 65 and older have Alzheimer’s dementia diagnoses, and this number is expected to increase to 13.8 million by 2026. Although there have been many attempts to slow down symptoms, scientists haven’t figured out how to stop the progression of the disease. Recently, however, an international team of researchers, co-led by scientists at the West China Hospital Sichuan University and the Institute for Bioengineering of Catalonia, discovered a novel approach to treating Alzheimer’s.
Alzheimer’s is caused by a buildup of abnormal proteins known as amyloid-beta plaques and tau tangles that disrupt the function of nerve cells in the brain. These clumps block nerve cell communication by preventing the usual propagation of messages between neurons in the brain. This results in the loss of connections between neurons, eventually leading to neuronal death.
Previously, research into treatments for Alzheimer’s focused on figuring out ways to inject drugs into the brain to remove these amyloid plaques. The main hurdle in such efforts has been breaching the highly defensive blood-brain barrier (BBB), a protective layer of cells and proteins that line the blood vessels in the brain. The BBB serves as a gatekeeper, directing the flow of traffic of chemical compounds in and out of the brain. The endothelial cells that make up the BBB are packed extremely close together, ensuring that the molecules the brain needs remain in the brain and those that are harmful are kept out. Because these cells have a lipid-based outer membrane, lipid-soluble substances that are small enough can cross the BBB. Several transport proteins exist in the BBB as well that allow for the transport of select types of molecules in and out of the brain. For years, researchers have attempted to leverage these inherent mechanisms of transport, utilizing nanoscopic lipid-soluble packages to deliver Alzheimer’s drug treatments into the brain. These packages contained the necessary characteristics for transport across the protective BBB: they were lipid-soluble and very small. They were therefore able to breach the protective BBB, allowing the Alzheimer’s drugs to enter the brain and treat the disease. This method, however, is still being researched and fine-tuned.
Meanwhile, these researchers in China and Spain have discovered a different way of approaching the search for an Alzheimer’s treatment, and that is to view the BBB not as a barrier to overcome but as a gateway in need of repair. Rather than focusing on ways to smuggle drugs into the brain, they sought to discover ways to get the amyloid-beta clumps out of the brain. Their research is based on an emerging hypothesis that Alzheimer’s is a result of a weakened BBB, leading to the accumulation of wastes in the brain that aren’t properly disposed of. These researchers discovered that instead of merely transporting drugs into the brain, the nanoparticles can act as drugs themselves, restoring the function of the BBB. Targeting endothelial LRP1, one of the transport proteins embedded in the BBB, the nanoparticles act as “tiny engineers of cellular behavior,” manipulating the LRP1 proteins to efficiently remove the beta-amyloid clumps from the brain.
After just three injections of this new intervention, researchers found that mice with genes that mimic those of Alzheimer’s exhibited a reduction in key symptoms associated with the disease. After just one injection alone, they found a 45% decrease in the beta-amyloid clumps, the hallmark of Alzheimer’s. At the completion of the therapy, the mice fully recovered their cognitive abilities, performing as well as their healthy peers in memory and learning tests.
According to Julia Dudley, head of research at Alzheimer’s Research UK, it is still unclear if this novel treatment will be effective on humans. The brain vasculature, or network of blood vessels, of mice is different from that of humans, and the current study looked specifically at repairing the brain vasculature of mice. However, this breakthrough adds to the growing evidence that repairing the BBB itself can be a more efficient and effective way of treating Alzheimer’s than attempting to breach its walls. More research into this new intervention method will hopefully lead to the production of marketable treatments that can decrease the prevalence of Alzheimer’s cases.
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