Whole brain single-cell transcriptomic map of neuroimmune in Alzheimer's disease

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 equilibrium between Aβ phagocytosis and extracellular vesicle (EV)-mediated Aβ secretion by microglia, the brain's innate immune cells, is critical for the propagation of Aβ plaques, neuritic dystrophy, and synaptic loss. Recently, our research demonstrated that microglia release extracellular vesicles containing Aβ, contributing to the expansion of Aβ plaques and dystrophic neurites. This process is exacerbated in microglia exhibiting dystrophic primary cilia. To further elucidate the neuroimmune mechanisms underlying neuroprotection, we developed a comprehensive map of myeloid cells in the AD brain, termed M-Galactic, utilizing 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 a nuanced understanding of the cellular landscape in AD.