Cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment.
Cell
; 185(26): 5028-5039.e13, 2022 12 22.
Article
em En
| MEDLINE
| ID: mdl-36516855
ABSTRACT
Cerebrospinal fluid (CSF) contains a tightly regulated immune system. However, knowledge is lacking about how CSF immunity is altered with aging or neurodegenerative disease. Here, we performed single-cell RNA sequencing on CSF from 45 cognitively normal subjects ranging from 54 to 82 years old. We uncovered an upregulation of lipid transport genes in monocytes with age. We then compared this cohort with 14 cognitively impaired subjects. In cognitively impaired subjects, downregulation of lipid transport genes in monocytes occurred concomitantly with altered cytokine signaling to CD8 T cells. Clonal CD8 T effector memory cells upregulated C-X-C motif chemokine receptor 6 (CXCR6) in cognitively impaired subjects. The CXCR6 ligand, C-X-C motif chemokine ligand 16 (CXCL16), was elevated in the CSF of cognitively impaired subjects, suggesting CXCL16-CXCR6 signaling as a mechanism for antigen-specific T cell entry into the brain. Cumulatively, these results reveal cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Neurodegenerativas
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Doença de Alzheimer
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Disfunção Cognitiva
Limite:
Aged
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Aged80
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Humans
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Middle aged
Idioma:
En
Revista:
Cell
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos