Alzheimer’s in a Dish Model Replicates Pathology, Including Inflammation
In This Article
- Neuroinflammation is the key biological response that leads to the death of brain cells, ultimately leading to cognitive impairment and dementia
- A Mass General research team has built on their previous development of a system that fully replicates the pathology behind Alzheimer’s disease to now include inflammation
- The team used the new model to find that blocking two receptors in microglial cells can prevent neuroinflammation—a finding that creates new opportunities for drug discovery
Neuroinflammation is the key biological response that leads to the death of brain cells, and ultimately to cognitive impairment and dementia. A Massachusetts General Hospital research team led by Rudolph Tanzi, PhD, vice-chair of the Mass General Neurology Department, and Doo Yeon Kim, PhD, assistant in Neuroscience, recently built upon their previous “Alzheimer’s in a dish” model, the first culture system to fully replicate the pathology behind familial Alzheimer’s disease (FAD). The model works by recapitulating the plaques and tangles typically seen in the brains of affected patients and now includes inflammation.
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Researchers added glia cells that that not only surround and support neurons, but also provide some immune system functions. They found that when human microglia were added to the model, they soon began to show structural changes signifying their activation and ultimately attacked neurons directly. This caused visible damage to key structures while levels of inflammatory factors rose significantly.
The team used the improved system to culture neural stem cells with FAD variants. They found that several weeks later, the neurons and astrocytes that had differentiated now contained elevated levels of amyloid-beta and tau, as well as inflammatory factors known to contribute to neuroinflammation. They also found that blocking two receptors in microglial cells—interferon receptor gamma and toll-like receptor 4—can prevent neuroinflammation.
Studies have shown that individuals may have many plaques and tangles in their brains with no symptoms until the onset of neuroinflammation causes exponentially more neurons to die. The new system’s ability to induce inflammation will allow for a more complete picture of Alzheimer’s pathology.
The team hopes this improved system will allow for better understanding of the timeline of pathological events that lead to dementia. It will also enable researchers to develop drugs that stop plaque deposition, tangle formation and the resultant neuroinflammation.
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