Normal aging, motor neurone disease, and Alzheimer’s disease are characterized by cortical changes in inflammatory cytokines

Anuradha Tennakoon, Viythia Katharesan, Ian Francis Musgrave, Simon A. Koblar, Richard Lewis Maxwell Faull, Maurice Anthony Curtis, Ian Johnson

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

The role of increased brain inflammation in the development of neurodegenerative diseases is unclear. Here, we have compared cytokine changes in normal aging, motor neurone disease (MND), and Alzheimer's disease (AD). After an initial analysis, six candidate cytokines, interleukin (IL)- 4, 5, 6, 10, macrophage inhibitory protein (MIP)-1α, and fibroblast growth factor (FGF)-2, showing greatest changes were assayed in post-mortem frozen human superior frontal gyri (n = 12) of AD patients, aging and young adult controls along with the precentral gyrus (n = 12) of MND patients. Healthy aging was associated with decreased anti-inflammatory IL-10 and FGF-2 levels. AD prefrontal cortex was associated with increased levels of IL-4, IL-5, and FGF-2, with the largest increase seen for FGF-2. Notwithstanding differences in the specific frontal lobe gyrus sampled, MND patients’ primary motor cortex (precentral gyrus) was associated with increased levels of IL-5, IL-6, IL-10, and FGF-2 compared to the aging prefrontal cortex (superior frontal gyrus). Immunocytochemistry showed that FGF-2 is expressed in neurons, astrocytes, and microglia in normal aging prefrontal cortex, AD prefrontal cortex, and MND motor cortex. We report that healthy aging and age-related neurodegenerative diseases have different cortical inflammatory signatures that are characterized by increased levels of anti-inflammatory cytokines and call into question the view that increased inflammation underlies the development of age-related neurodegenerative diseases.
Original languageEnglish
Pages (from-to)653-669
Number of pages17
JournalNeuroscience Research
Volume100
Issue number2
DOIs
Publication statusPublished - Feb 2022

Keywords

  • Alzheimer's disease
  • cytokine
  • fibroblast growth factor 2
  • human
  • motor neurone disease
  • postmortem
  • RRID:AB_221448
  • RRID:AB_2636877
  • RRID:AB_2732856
  • RRID:AB_2732857
  • RRID:AB_2811722
  • RRID:AB_354307
  • RRID:AB_869005
  • RRID:SCR_002865

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