Spatial Single-cell Transcriptomic Map of Neuroimmune in Alzheimer's Brain

초록

Alzheimer's disease (AD) is characterized by the extracellular deposition of amyloid-beta (Aβ) plaques, which are closely associated with activated glial cells, dystrophic neurites, and neurofibrillary tangles. The balance between Aβ phagocytosis and extracellular vesicle (EV)-mediated Aβ secretion by microglia, the brain's innate immune cells, is crucial for the propagation of Aβ plaques, neuritic dystrophy, and synaptic loss. Our recent research has demonstrated that microglia release extracellular vesicles containing Aβ, thereby contributing to the expansion of Aβ plaques and dystrophic neurites. This process is further exacerbated in microglia exhibiting dystrophic primary cilia. To elucidate the neuroimmune mechanisms underlying neuroprotection, we developed a comprehensive map of myeloid cells in the AD brain, termed M-Galactic, using single-cell RNA sequencing data. Additionally, we constructed a spatial single-cell map (3M-Galactic) by deconvoluting and projecting the M-Galactic data and integrating it with the whole-brain Aβ distribution obtained through iACT brain clearing and staining techniques. The 3M-Galactic map reveals the global distribution of heterogeneous neuroimmune cells and their correlation with Aβ heterogeneity and distribution, providing an advanced understanding of the cellular landscape in AD.