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11 Dec 2020 It is difficult to isolate large quantities of microglia from human brain. That’s why scientists still know little about the different ways these cells rear up in health and disease. A new single-cell not single-nucleus RNA-sequencing study led by Philip De Jager at Columbia University, New York, sheds some light on this. It analyzed the largest number of microglia yet, totaling more than 16,000, isolated from the brains of people with Alzheimer’s disease and normal cognition. In the November 30 Nature Communications, the authors describe nine distinct transcriptional states found in all brain samples. At least 80 percent of microglia fell into one of two homeostatic subtypes; that was true even in AD brains. Seven other subtypes comprised less than 5 percent of brain microglia each. Their proportion varied by individual and by disease state. One subtype, dubbed cluster 7, expressed numerous genes associated with AD; curiously, it was nearly gone from AD brain.

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