Inflammatory protein associations with brain MRI measures: Framingham Offspring Cohort

Alzheimers Dement. 2024 Nov;20(11):7465-7478. doi: 10.1002/alz.14147. Epub 2024 Sep 16.

Abstract

Introduction: Brain magnetic resonance imaging (MRI) and inflammatory biomarkers are crucial for investigating preclinical neurocognitive disorders. Current investigations focus on a few inflammatory markers. The study aims to investigate the associations between inflammatory biomarkers and MRI measures and to examine sex differences among the associations in the Framingham Heart Study.

Methods: Dementia and stroke-free participants underwent OLINK Proteomics profiling and MRI measurements within 5 years. Pairwise cross-sectional analysis assessed 68 biomarkers with 13 brain MRI volumes, adjusting for covariates and familial correlations.

Results: Elevated CDCP1, IL6, OPG, and 4E.BP1 were related to smaller total cerebral brain volume (TCBV), whereas higher HGF, IL8, and MMP10 were associated with smaller TCBV, total and frontal white matter volumes. Higher SCF and TWEAK were associated with larger TCBV. In sex-stratified analyses, associations were observed exclusively among males.

Discussion: We report several associations between inflammatory biomarkers and brain volumes, highlighting different associations within sex subgroups.

Highlights: Higher CDCP1, IL6, OPG, and 4E.BP1 levels were associated with smaller TCBV. Higher levels of HGF, IL8 and MMP10 were associated with smaller TCBV, CWV and FWV. Higher levels of SCF and TWEAK, were associated with larger TCBV. Significance diminished in models adjusting for CVD risk factors. Associations were observed exclusively in males.

Keywords: Alzheimer's disease; MRI; aging; biomarkers; cognitive aging; dementia.

MeSH terms

  • Aged
  • Biomarkers*
  • Brain* / diagnostic imaging
  • Brain* / pathology
  • Cohort Studies
  • Cross-Sectional Studies
  • Cytokine TWEAK
  • Female
  • Humans
  • Inflammation / diagnostic imaging
  • Interleukin-6 / blood
  • Interleukin-8
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Proteomics
  • Sex Factors

Substances

  • Biomarkers
  • Interleukin-6
  • Interleukin-8
  • Cytokine TWEAK