Intercellular Signaling And Synaptic Deconstruction Uncovered By Single-Cell And Spatial Transcriptomics In An AD Tauopathy Model
Alzheimer’s disease, a leading cause of dementia, involves complex changes in the brain that are not fully understood. Recent research using advanced techniques has shed light on how the disease progresses at a cellular level. Scientists employed methods that allow them to examine the genetic activity of individual brain cells and map their locations within brain tissue, providing an incredibly detailed view of the disease’s impact. In a model mimicking human-like Alzheimer’s pathology, researchers discovered new indicators of the disease linked to abnormal tau protein. They found that changes in tau protein, along with aging, disrupt how brain cells communicate with each other. This communication relies on molecules called ligands binding to receptors on other cells, triggering specific responses. The study also revealed alterations in the systems that control which genes are active in cells, affecting their overall function. Crucially, the findings highlighted significant changes in cell communication involving signals that use glutamate, a vital chemical messenger for brain function, and Netrin signaling, which is important for guiding and maintaining connections between brain cells. These disruptions contribute to the breakdown of synapses, the critical junctions where neurons transmit information. This work reinforces the idea that problems with these neuronal connections are an early and crucial event in Alzheimer’s disease, offering potential new targets for developing treatments.
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