Receptors for pro‐resolving mediators are increased in Alzheimer's disease brain
Open accessAbstract
Neuroinflammation is a key element of AD pathology and conceivably a result of a disturbed resolution. Resolution of inflammation is an active process which is strictly orchestrated following the acute inflammatory response after removal of the inflammatory stimuli. Acute inflammation is actively terminated by specialized pro‐resolving mediators (SPMs) thereby promoting healing and return to homeostasis. Failed resolution may contribute to persistent neuroinflammation and aggravate AD pathology. BLT1 (leukotriene B 4 receptor) and ChemR23 (chemerin receptor 23) are receptors for the SPM resolvin (Rv) E1 and are important clinical targets for ending inflammation. In AD, the levels of SPMs are decreased, and pro‐inflammatory mediators are increased. In the current study, the distribution of BLT1 and ChemR23 receptors in control brains and in AD as well as correlations with AD pathology was examined for the first time. BLT1 and ChemR23 were analyzed in different regions of post‐mortem human brain from cases with AD, early‐onset AD and mild cognitive impairment (MCI) and healthy controls, using western blotting and immunohistochemistry. BLT1 and ChemR23 were detected in neurons and glial cells in all examined regions of the human brain, with markedly higher levels in AD than in controls. The receptor levels correlated with the density of staining for the inflammation markers HLA‐DR and YKL‐40 for microglia and astrocytes, respectively, and elevated staining coincided with high Braak stages in AD. The relative staining densities of these receptors were higher in the basal forebrain, cingulate gyrus and hippocampal regions compared to the cerebellum and frontal cortex (BA46). In conclusion, alterations in the expression of the resolution receptor BLT1 in AD have not been reported previously and the changes in both BLT1 and ChemR23 suggest a disturbed resolution pathway in several regions of the AD brain that may play a role in disease pathology.
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Numerous studies have identified abnormality of inflammation resolution in AD, including abnormality in the profile of SPMs and its receptors.
“Numerous studies have identified abnormality of inflammation resolution in AD, including the abnormality in the profile of SPMs and its receptors.175,425,426”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [426]
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- Authors
- Emre, C., Hjorth, E., Bharani, K., Carroll, S., Granholm, A., & Schultzberg, M.
- Affiliations
- Karolinska Institutet (SE)
- Medical University of South Carolina (US)
- University of Denver (US)
- Corresponding author
- Schultzberg, Marianne
- Venue
- Brain Pathology
- Publisher
- Wiley
- Published
- 2020-01-21
- Volume
- 30
- Issue
- 3
- Pages
- 614-640
- ISSN
- 1015-6305 (ISSN-L)
- 1750-3639
- PMC
- PMC8018009
- OpenAlex
- W2998971756
- Cited by
- 60
- References
- 94
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 8 · 2023: 8 · 2022: 12 · 2021: 16 · 2020: 6
- FWCI
- 6.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain Pathology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Stiftelsen för Gamla Tjänarinnor
- Vetenskapsrådet (22743, 22744)
- Gun och Bertil Stohnes Stiftelse
- Knut och Alice Wallenbergs Stiftelse
- National Institute on Aging (R21AG048631)
- Alzheimerfonden
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- Alzheimer's disease, inflammation resolution, specialized pro-resolving mediators, BLT1, leukotriene B4 receptor, ChemR23, resolvin E1, neuroinflammation, microglia, astrocytes, HLA-DR, YKL-40, Braak stages, mild cognitive impairment, hippocampus, cingulate gyrus, basal forebrain, receptor expression
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Astrocytes, Brain, Female, Humans, Inflammation, Male, Middle Aged, Neurons, Receptors, Leukotriene B4, Receptors, Chemokine
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