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Can a novel Alzheimer’s therapy target multiple aspects of the disease at the same time?
Giuseppe Battaglia, Ph.D.
Fundacio Institut de Bioenginyeria de Catalunya
Barcelona, Spain
Background
Studies show that brain inflammation (neuroinflammation) and loss of brain blood vessel (cerebrovascular) function may represent early changes in Alzheimer’s. These changes, which can lead to nerve cell damage and death, involve a specialized structure called the blood brain barrier (BBB). The BBB helps maintain a healthy brain environment by tightly regulating what goes in and out of the brain from the circulating blood. It is composed of different cells, including endothelial cells, that help transport blood, nutrients and oxygen into the brain and harmful proteins (such as Alzheimer’s-related beta-amyloid and tau) out of the brain.
According to current research, an endothelial cell protein called LRP1 (low-density lipoprotein receptor-related protein) may play an important role in clearing unwanted proteins. Studies have found that neuroinflammation may reduce LRP1 in endothelial cells and lead to tau and amyloid clumping in the brain. This clumping, in turn, can promote more inflammation and BBB damage, and the eventual loss of brain function. Such findings suggest the need for therapies that can target both neuroinflammation and endothelial cell damage at an early stage, before they lead to cognitive decline. However, BBB-related treatments have been challenging to develop, as researchers have found it difficult to deliver therapies that bind to or cross the BBB effectively.
Research Plan
Dr. Giuseppe Battaglia and colleagues will test a new therapeutic technique for Alzheimer’s that targets the blood-brain barrier. Using nanotechnology, they will engineer a tiny molecular “carrier” that can deliver multiple therapeutic compounds to the BBB and brain – compounds that target both neuroinflammation and the loss of LRP1 in BBB endothelial cells. The researchers will then test whether this therapy can prevent brain inflammation, amyloid and tau clumping, and cognitive decline in mice engineered to develop Alzheimer’s-like brain changes.
Impact
Results from this project could help clarify the BBB’s role in Alzheimer’s. They could also promote drug therapies that more effectively treat Alzheimer’s by targeting multiple facets of the disease at once.
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