Immune System Protein Reverses Alzheimer’s Disease in Mice

Background

The immune system is closely involved with the pathology of Alzheimer’s disease. In healthy brains, immune cells called microglia work to destroy or clear away harmful substances in the brain. However, the gradual accumulation of a toxic protein called amyloid-beta can disrupt microglial function, causing them to release potentially-harmful inflammatory molecules. The inflammatory pathways activated by microglial signaling contribute to the development and progression of Alzheimer’s disease. A 2012 study showed that inhibiting some of these pathways can combat Alzheimer’s in animal models.

A protein called interleukin-33 (IL-33) is an important mediator of inflammation and is involved with multiple infections and autoimmune diseases. Genetic studies have demonstrated that people with certain variants in the IL-33 gene have an increased risk of Alzheimer’s. Additionally, the brains of people with Alzheimer’s have decreased levels of IL-33 gene expression compared to healthy brains. This has led some to speculate that lower levels of IL-33 may promote the buildup of amyloid-beta that occurs in Alzheimer’s disease.

New Study

Research published recently in the journal PNAS attempted to address whether IL-33 could be a therapeutic target for Alzheimer’s. The researchers used mice that were genetically designed to simulate Alzheimer’s pathology and injected them with the IL-33 protein. After two days of injections, the mice showed significantly improved long-term potentiation, the process strengthening connections between neurons that is critical for learning and memory. After seven days, the mice also had an improved response to fear conditioning, a test of contextual memory retrieval. Additionally, the mice had approximately 20% lower levels of amyloid-beta plaques in their brains. The researchers demonstrated that this reduction was due to the activation of alternate inflammatory pathways, which enhanced the ability of microglia to destroy the plaques.

Additional research is needed to determine the mechanism by which IL-33 improves Alzheimer’s symptoms in these mice. It is also unclear whether these results will generalize to humans, as the mouse models are more similar to human early-onset Alzheimer’s disease and bear significant differences from the more common late-onset form. However, the research presents an intriguing new approach to combatting Alzheimer’s by enhancing the brain’s own immune system.

 

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