Fig. 1
The HuMi_Aged and its relationship to genetic risk of AD. a Scatter plot depicting the distribution of gene expression values between the bulk DLPFC (N = 540) and the isolated microglia (N = 10). Each dot represents a gene. The X and the Y axes show normalized expression values. One thousand fifty four genes have been identified to be preferentially expressed by microglia (based on the differences in gene expression between the isolated microglia and the bulk cortical tissue, FC > 4) in the aged human brain (dark blue dots). This set of genes has been coined the HuMi_Aged gene set. The HuMi_Aged gene set contained many of the previously established microglia markers in the brain (black dots), such as CD74, CX3CR1, P2RY12, TREM2 or GPR34. b Scatter plot showing the distribution of AD risk genes (black dots) in the transcriptomic universe defined by the bulk cortical and the microglial RNA-Sequencing datasets. Each dot represents a gene. The X and the Y axes show normalized expression values. By using an overrepresentation test, the HuMi_Aged gene set (blue dots) was found to be significantly enriched in Alzheimer’s disease risk genes (black dots; enrichment p-value = 4.1e-05). The HuMi_Aged included AD risk genes, such as CD33, TREM2, INPP5D, APOC1 or SCIMP, while other AD risk genes (e.g., BIN1 or TREML2) were found to be not specific to microglia in the aged brain. c APOE ε2 was associated with reduced expression of HuMi_Aged in the bulk tissue level data (N = 540). DLPFC dorsolateral prefrontal cortex, FC fold change
