Astrocyte priming enhances microglial Aβ clearance and is compromised by APOE4
- Authors
- Lee, Se-In; Yu, Jichang; Lee, Hyein; Kim, Buyun; Jang, Min Jun; Jo, Hyeonbin; Kim, Na Yeon; Pak, Malk Eun; Kim, Jae Kwang; Cho, Sukhee; Won, Hong-Hee; Kim, Min Soo; Gao, Fan; Go, Younghoon; Seo, Jinsoo
- Issue Date
- 2025-08
- Publisher
- Nature Publishing Group
- Citation
- Nature Communications, v.16, no.1
- Abstract
- The innate immune system can develop a form of memory called priming, where prior exposure to a stimulus enhances subsequent responses. While well-characterized in peripheral immunity, its function in brain-resident cells such as astrocytes under non-disease conditions remains unclear. Here we show that human astrocytes derived from the induced pluripotent stem cells of healthy female donors, but not microglia, acquire a primed state following transient immune stimulations. Upon subsequent exposure to amyloid-beta (A beta), these astrocytes secrete elevated levels of cytokines and promote microglial A beta uptake. In contrast, astrocytes carrying the Alzheimer's disease (AD) risk allele APOE4 exhibit reduced priming and fail to support microglial phagocytosis. These findings are validated in astrocyte-microglial co-cultures, cerebral organoids, and male mice, where astrocyte priming enhances A beta clearance in an APOE4-sensitive manner. Our findings identify astrocytic immune memory as a modulator of microglial function and A beta pathology, providing insights into how early protective responses in AD may be disrupted by genetic risk factors.
- Keywords
- PATHWAY; GENE
- URI
- https://pubs.kist.re.kr/handle/201004/153115
- DOI
- 10.1038/s41467-025-62995-1
- Appears in Collections:
- KIST Article > Others
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