A transcriptomic atlas of aged human microglia.
With a rapidly aging global human population, finding a cure for late onset neurodegenerative diseases has become an urgent enterprise. However, these efforts are hindered by the lack of understanding of what constitutes the phenotype of aged human microglia-the cell type that has been strongly implicated by genetic studies in the pathogenesis of age-related neurodegenerative disease. Here, we establish the set of genes that is preferentially expressed by microglia in the aged human brain. This HuMi_Aged gene set captures a unique phenotype, which we confirm at the protein level. Furthermore, we find this gene set to be enriched in susceptibility genes for Alzheimer's disease and multiple sclerosis, to be increased with advancing age, and to be reduced by the protective APOEε2 haplotype. APOEε4 has no effect. These findings confirm the existence of an aging-related microglial phenotype in the aged human brain and its involvement in the pathological processes associated with brain aging.
|Year of Publication
2018 02 07
|PubMed Central ID
R56 NS089674 / NS / NINDS NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
R01 AG043617 / AG / NIA NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
R01 AI130547 / AI / NIAID NIH HHS / United States
R01 NS089674 / NS / NINDS NIH HHS / United States