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Nat Commun. 2018 Feb 7;9(1):539. doi: 10.1038/s41467-018-02926-5.

A transcriptomic atlas of aged human microglia.

Author information

1
Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York City, NY, 10032, USA.
2
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, 02142, USA.
3
School of Mathematics and Statistics, The University of Sydney, Sydney, New South Wales, 2006, Australia.
4
Massachusetts General Hospital, Boston, MA, 02114, USA.
5
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
6
Pacific Northwest National Laboratory, Richland, WA, 99354, USA.
7
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA.
8
Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York City, NY, 10032, USA. pld2115@cumc.columbia.edu.
9
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, 02142, USA. pld2115@cumc.columbia.edu.
10
Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York City, NY, 10032, USA. emb2280@cumc.columbia.edu.
11
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, 02142, USA. emb2280@cumc.columbia.edu.

Abstract

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.

PMID:
29416036
PMCID:
PMC5803269
DOI:
10.1038/s41467-018-02926-5
[Indexed for MEDLINE]
Free PMC Article

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