Scientists at Massachusetts General Hospital (MGH) have developed a new 3D model of Alzheimer’s disease (AD) that offers insights into the role of immune cells in the progression of the disease. The model mimics the interactions between brain cells and immune cells, particularly T cells, which can enter the brain and exacerbate AD pathology.
The study, published in Nature Neuroscience, demonstrates that as AD pathology accumulates in the brain, specific types of immune cells called CT8+ T cells increase and contribute to the destruction of brain cells through neuroinflammation. The researchers also identified the molecular mechanisms that drive the infiltration of T cells into the brain and showed that blocking these mechanisms reduced the harmful effects of T cell infiltration.
This new model could pave the way for the development of targeted therapies for AD that aim to prevent immune cell infiltration in the brain. By observing the behavior of distinct cell types in the disease context, the researchers hope to identify strategies for intervention that could lead to more effective treatments.
The model consists of a 3D human neuroimmune axis, which includes stem-cell derived neurons, astrocytes, microglia, and peripheral immune cells. This extension of previous work by the research team provides a more physiologically relevant representation of AD in a lab setting.
The team also discovered a pathway between a chemokine called CXCL10 and a chemokine receptor called CXCR3 that plays a critical role in regulating T cell infiltration. By blocking this pathway, the researchers were able to prevent T cell infiltration and reduce neurodegeneration in AD cultures.
What makes these findings particularly exciting is the identification of a new drug target on T cells that could be more accessible for novel treatments. Traditionally, it has been challenging to develop drugs that can penetrate the brain, but targeting immune cells outside of the brain may offer new opportunities for therapeutic intervention.
Overall, this research provides valuable insights into the role of immune cells in Alzheimer’s disease and highlights potential avenues for developing effective treatments. By understanding the intricate interactions between brain cells and immune cells, researchers may be able to develop strategies to halt the progression of the disease and mitigate its devastating cognitive effects. Further experiments with this 3D model may identify additional therapeutic targets and advance our understanding of Alzheimer’s disease.
