I first saw a summary of this at the Broad Institute websites ("Researchers map brain cell changes in Alzheimer’s disease" https://www.broadinstitute.org/news/researchers-map-brain-cell-changes-alzheimers-disease) which provided a nice summary of the article and a few statements from the researchers. The original article was published in February in Nature Neuroscience:
Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer’s disease
- Hu Zeng, et al., Nature Neuroscience volume 26, pages 430–446 (2023)
Using a technique called STARmap PLUS, the researchers used high-resolution spatial transcriptomics and specific protein detection in tissue sections from a mouse model of Alzheimer's. From the abstract:
It reveals a core–shell structure where disease-associated microglia (DAM) closely contact amyloid-β plaques, whereas disease-associated astrocyte-like (DAA-like) cells and oligodendrocyte precursor cells (OPCs) are enriched in the outer shells surrounding the plaque-DAM complex. Hyperphosphorylated tau emerges mainly in excitatory neurons in the CA1 region and correlates with the local enrichment of oligodendrocyte subtypes. The STARmap PLUS method bridges single-cell gene expression profiles with tissue histopathology at subcellular resolution, providing a tool to pinpoint the molecular and cellular changes underlying pathology.
The mapping was able to identify the location of protein expression of 2,700 genes and with antibodies to tag specific proteins their location - all done with 3-D positioning within tissue slices. Based on their observations, the researchers felt the microglia were activated near the plaques to form protective shells as part of an inflammatory response rather than being activated elsewhere and recruited to the plaques. However, they have not yet fully determined the role of the microglia cells within the overall disease.
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