Innovations advancing our understanding of microglia in Alzheimer's disease: From in vitro to in vivo models

Microglial research has been limited because of poor conservation of microglial states across species, and in vitro models having distinct transcriptomic profiles to native microglia in vivo. Advances in technologies, such as single-cell RNA sequencing, have allowed for a deeper understanding of microglial heterogeneity in healthy states and neurodegeneration. The transplantation of microglia derived from human pluripotent stem cells into organoids or mouse brains better mimics the 3D physiological microenvironment, allowing for restoration of morphology and phenotypic states similar to native microglia. Xenotransplantation mouse models and organoids offer a valuable platform to better define the role microglia play in neurodegeneration. AbstractMicroglia have been implicated in Alzheimer's disease (AD) pathogenesis through the identification of risk factor genes that are specifically or predominantly expressed in this cell type. Additional evidence suggests that microglia undergo dramatic morphological and phenotypic state changes during AD progression, as observed in human post-mortem tissue and animal model research. Although valuable, these studies are often hampered by either representing one time point in human tissue (end point) or because of the lack of conservation between species of microglial transcriptomes, proteomes and cell states. Thus, the development and application of novel human model systems have been beneficial in the study of microglia in neurodegenerati...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: REVIEW Source Type: research