Associations of neuroinflammatory IL-6 and IL-8 with brain atrophy, memory decline, and core AD biomarkers - in cognitively unimpaired older adults

Brain Behav Immun. 2023 Oct:113:56-65. doi: 10.1016/j.bbi.2023.06.027. Epub 2023 Jul 1.


Concentrations of pro-inflammatory cytokines -interleukin-6 (IL-6) and interleukin-8 (IL-8) - are increased with age and in Alzheimer's disease (AD). It is not clear whether concentrations of IL-6 and IL-8 in the central nervous system predict later brain and cognitive changes over time nor whether this relationship is mediated by core AD biomarkers. Here, 219 cognitively healthy older adults (62-91 years), with baseline cerebrospinal fluid (CSF) measures of IL-6 and IL-8 were followed over time - up to 9 years - with assessments that included cognitive function, structural magnetic resonance imaging, and CSF measurements of phosphorylated tau (p-tau) and amyloid-β (Aβ-42) concentrations (for a subsample). Higher baseline CSF IL-8 was associated with better memory performance over time in the context of lower levels of CSF p-tau and p-tau/Aβ-42 ratio. Higher CSF IL-6 was related to less CSF p-tau changes over time. The results are in line with the hypothesis suggesting that an up-regulation of IL-6 and IL-8 in the brain may play a neuroprotective role in cognitively healthy older adults with lower load of AD pathology.

Keywords: AD biomarkers; Cerebrospinal fluid; Cognitively unimpaired older adults; Interleukin-6; Interleukin-8; Longitudinal MRI.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Atrophy / pathology
  • Biomarkers / cerebrospinal fluid
  • Brain / pathology
  • Cognitive Dysfunction* / pathology
  • Humans
  • Interleukin-6
  • Interleukin-8
  • Memory Disorders / pathology
  • Peptide Fragments / cerebrospinal fluid
  • tau Proteins / cerebrospinal fluid


  • Interleukin-6
  • Interleukin-8
  • tau Proteins
  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments