A study published in Nature Neuroscience has identified Plexin-B1, encoded by the PLXNB1 gene, as a regulator of peri-plaque glial nets in Alzheimer’s disease (AD). Researchers highlighted the significance of Plexin-B1 in astrocytes and its role in enhancing glial responses around amyloid plaques.
Alzheimer’s disease remains a major challenge due to the lack of effective treatments. While amyloid plaques are central to AD pathology, the mechanisms of amyloid-beta (Aβ) deposition, clearance, and plaque compaction are not well understood. This study builds on recent findings about microglial phagocytic activity, which promotes plaque compaction and limits neurotoxicity.
Researchers explored gene expression databases and conducted various analyses, finding that Plexin-B1 was predominantly expressed in astrocytes within the central nervous system. Using a Plxnb1 knockout mouse model, they observed that the absence of Plexin-B1 resulted in smaller, more compact glial nets and increased plaque coverage by glial cells. This deletion also improved synaptic and neuronal functions while reducing neuroinflammation and cell death.
As reported by News Medical, bulk and single-cell RNA sequencing further revealed significant gene expression changes associated with enhanced synaptic function and decreased inflammation in the absence of Plexin-B1. The findings suggest that inhibiting Plexin-B1 could be a novel therapeutic approach for Alzheimer’s disease.