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Cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment.
Piehl, Natalie; van Olst, Lynn; Ramakrishnan, Abhirami; Teregulova, Victoria; Simonton, Brooke; Zhang, Ziyang; Tapp, Emma; Channappa, Divya; Oh, Hamilton; Losada, Patricia M; Rutledge, Jarod; Trelle, Alexandra N; Mormino, Elizabeth C; Elahi, Fanny; Galasko, Douglas R; Henderson, Victor W; Wagner, Anthony D; Wyss-Coray, Tony; Gate, David.
Afiliação
  • Piehl N; The Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • van Olst L; The Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Ramakrishnan A; The Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Teregulova V; The Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Simonton B; The Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Zhang Z; The Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Tapp E; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
  • Channappa D; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
  • Oh H; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA; Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA; Graduate Program in Stem Cell and Regenerative Medicine, Stanford University, Stanford, CA, USA.
  • Losada PM; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
  • Rutledge J; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA; Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Trelle AN; Department of Psychology, Stanford University, Stanford, CA, USA.
  • Mormino EC; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA; Department of Psychology, Stanford University, Stanford, CA, USA.
  • Elahi F; Departments of Neurology and Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, La Jolla, CA, USA.
  • Galasko DR; Department of Neurosciences, University of California at San Diego, La Jolla, CA, USA.
  • Henderson VW; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
  • Wagner AD; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA; Department of Psychology, Stanford University, Stanford, CA, USA.
  • Wyss-Coray T; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA; Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA; The Phil an
  • Gate D; The Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Electronic address: dgate@northwestern.edu.
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Neurodegenerativas / Doença de Alzheimer / Disfunção Cognitiva Limite: Aged / Aged80 / Humans / Middle aged Idioma: En Revista: Cell Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Neurodegenerativas / Doença de Alzheimer / Disfunção Cognitiva Limite: Aged / Aged80 / Humans / Middle aged Idioma: En Revista: Cell Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos