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Author Notes:

Correspondence: William T. Hu wthu@emory.edu; william.hu@emory.edu

WH, JH, and UG contributed to conception and design of the study.

WH, JH, TO, UG, AK, JH-M, AA, and WT organized the dataset.

WH performed the statistical analysis. WH and JH wrote sections of the manuscript.

TO, UG, JH-M, AA, and WT contributed to the revision of the manuscript.

All authors read and approved the submitted version.

We would like to thank Drs. Jonathan D. Glass, Stewart A. Factor, and Neil S. Lava for their assistance in recruitment.

WH has a patent on the use of CSF biomarkers to diagnose FTLD-TDP (US 9,618,522); has received research support from Avid Radiopharmaceuticals (Philadelphia, PA) and Fujirebio US (Malvern, PA); serves as a consultant to AARP, Inc, Locks Law Firm, Interpleader Law, and Roche Diagnostics USA, ViveBio LLC; has received travel support from Hoffman-LaRoche and Abbvie.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Research Funding:

This study was sponsored by the NIH K23AG042856 (WH), R21AG043885 (WH), R01AG054046 (WH), K23MH095679 (AA), R01MH116695 (WT), I01BX01506 (WT), the Patterson Family Foundation, and the Bumpus Foundation (JH-M).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • inflammaging
  • neuroinflammation and neurodegeneration
  • IP10
  • IL10
  • IL8
  • Alzheimer's disease
  • Parkinsons disease (PD)
  • dementia with Lewy bodies (DLB)
  • AGE

CSF Cytokines in Aging, Multiple Sclerosis, and Dementia


Journal Title:

Frontiers in Immunology


Volume 10


, Pages 480-480

Type of Work:

Article | Final Publisher PDF


Inflammation is a common process involved in aging, multiple sclerosis (MS), and age-related neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), but there is limited evidence for the effects of aging on inflammation in the central nervous system. We collected cerebrospinal fluid (CSF) from 105 healthy control subjects representing a wide age range (23-86), and analyzed levels of cytokines associated innate immunity (TNF-α) and different T-helper subtypes: interferon-gamma induced protein 10 (IP-10) for Th1, interleukin-10 (IL-10) for Th2, and interleukin 8 (IL-8/CXCL8) for Th17. We show that CSF levels of TNF-α, IP-10, and IL-8 all increased linearly with age, but levels of IL-10 demonstrated a U-shaped relationship with age. We further found greater age-related increases in TNF-α, IL-10, and IL-8 relative to increases in IP-10 levels, consistent with a shift from Th1 to other inflammatory phenotypes. Finally, when we analyzed the same four cytokines in people with neurological disorders, we found that MS and AD, but not PD or dementia with Lewy bodies, further accentuated the age-related shift from Th1- to non-Th1-related cytokines. We propose that CSF cytokine levels represent powerful surrogates of brain inflammation and aging, and some, but not all, neurological disorders accelerate the shift away from Th1 phenotypes.

Copyright information:

© 2019 Hu, Howell, Ozturk, Gangishetti, Kollhoff, Hatcher-Martin, Anderson and Tyor.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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