Pattern of interleukin-6 receptor complex immunoreactivity between cortical regions of rapid autopsy normal and Alzheimer's disease brain
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Published on: May 19, 2022
Harald Hampel1, Andreas Haslinger, Michael Scheloske
1Alzheimer Memorial Centre, Geriatric Psychiatric Branch, Dementia Research Section, Dept. of Psychiatry Ludwig-Maximilian University, 80336 Munich, Germany. hampel@psy.med.uni-muenchen.de
Insights
The interleukin-6 receptor complex (IL-6RC) shows altered expression patterns in Alzheimer's disease (AD) brains. These changes in IL-6, IL-6R, and gp130 support a role for IL-6 in AD.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- The interleukin-6 receptor complex (IL-6RC) is implicated in brain neuroregulation and immunity.
- Its specific role in Alzheimer's disease (AD) pathophysiology remains hypothesized.
Purpose of the Study:
- To investigate the expression patterns of the IL-6 receptor complex (IL-6RC) in the brains of AD patients.
- To compare these patterns with those in healthy controls (HC).
Main Methods:
- Utilized a novel immunocytochemical protocol on rapid autopsy brain sections.
- Examined expression of IL-6, IL-6 receptor (IL-6R), and gp130 across five cortical regions.
- Compared expression in Braak IV-V staged AD patients with age-matched HC.
Main Results:
- Established baseline IL-6RC expression in normal brain tissue.
- Observed altered IL-6 expression in AD parietal and occipital cortices.
- Found significantly increased IL-6R expression in AD frontal and occipital cortices, with decreases in temporal cortex and cerebellum.
Conclusions:
- The study reveals altered cortical immunoreactivity of the IL-6RC in AD.
- Findings support the hypothesis that IL-6 plays a role in AD pathophysiology.
Abstract:
Involvement of the interleukin-6 receptor complex (IL-6RC) in neuroregulatory and immunological processes of the brain and particularly in Alzheimer's disease (AD) has been hypothesized. The functionally active IL-6RC consists of the cytokine IL-6, which acts through the ligand binding IL-6R and the signal transducing gp130. Using a new immunocytochemical protocol on rapid autopsy cryostat brain sections we studied the expression of the IL-6RC in Braak IV-V staged AD patients compared to normal age-matched controls (HC) across five different cortical regions. Inter-rater reliability of the method was high. The "baseline" expression in normal human brain was determined for IL-6,IL-6R and gp130 in all cortical regions. In normal tissue IL-6 expression was lower in parietal cortex. Higher IL-6R expression was shown in frontal, occipital and parietal cortex, lower expression in temporal cortex and cerebellum. In AD IL-6 expression levels were generally increased in parietal cortex and decreased in occipital cortex compared to controls. IL-6R expression levels were strongly increased in AD frontal and occipital cortex and decreased in temporal cortex and cerebellum. Our findings indicate an altered cortical immunoreactivity pattern of the functional IL-6RC in AD supporting the hypothesis of a disease-related role of IL-6 in AD pathophysiology.
