Expression of Macrophage Inflammatory Protein 1-α is Elevated in Alzheimer's Vessels and is Regulated by Oxidative Stress
Abstract
Inflammatory mediators are highly expressed in the Alzheimer's disease (AD) brain. We have shown that in AD the cerebral microcirculation is a rich source of cytokines and chemokines including interleukins (IL) 1beta, IL-6, IL-8, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1. However, the factors that regulate expression of these inflammatory proteins have not been defined. The objective of this study is to compare expression of macrophage inflammatory protein 1-alpha (MIP-1alpha) in brain microvessels isolated from AD patients to vessels from age-matched controls and further to determine whether expression of MIP-1alpha in brain endothelial cells is altered by oxidative stress. The data show that brain AD-derived microvessels express high levels of MIP-1alpha mRNA and release high levels of MIP-1alpha protein compared to brain microvessels isolated from controls. Treatment of brain endothelial cell cultures with menadione, a superoxide releasing compound, hydrogen peroxide, lipopolysacharride, or oxidatively modified low density lipoproteins (LDL) (Ox-LDL, HNE-LDL) results in a dose- dependent increase in MIP-1alpha mRNA levels and MIP-1alpha release into the media. These results suggest that oxidative and lipid insults to the brain microvasculature are likely to contribute to the inflammatory milieu of the AD brain.
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CXCL10 and CCL3 were found to be elevated in AD patients and associated with neurological symptoms.
“Importantly, CXCL10 and CCL3 were found to be elevated in AD patients and associated with neurological symptoms (55–57).”
From The effect of Abi3 locus deletion on the progression of Alzheimer’s disease-related pathologies (2023) · cites this paper as [55]
CXCL10 and CCL3 were found to be elevated in patients with AD and associated with neurological deficits.
“were found to be elevated in patients with AD and associated with neurological deficits (57–60).”
From Deletion of <i>Abi3</i> gene locus exacerbates neuropathological features of Alzheimer’s disease in a mouse model of Aβ amyloidosis (2021) · cites this paper as [60]
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Additional file 2 of Neurofilament light chain in the vitreous humor of the eye
Subramanian, M. L., Vig, V., Chung, J., Fiorello, M. G., Xia, W., Zetterberg, H., Blennow, K., Zetterberg, M., Shareef, F., Siegel, N. H., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12972148
Additional file 4 of Neurofilament light chain in the vitreous humor of the eye
Subramanian, M. L., Vig, V., Chung, J., Fiorello, M. G., Xia, W., Zetterberg, H., Blennow, K., Zetterberg, M., Shareef, F., Siegel, N. H., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12972154
Additional file 1 of Neurofilament light chain in the vitreous humor of the eye
Subramanian, M. L., Vig, V., Chung, J., Fiorello, M. G., Xia, W., Zetterberg, H., Blennow, K., Zetterberg, M., Shareef, F., Siegel, N. H., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12972145
Additional file 5 of Neurofilament light chain in the vitreous humor of the eye
Subramanian, M. L., Vig, V., Chung, J., Fiorello, M. G., Xia, W., Zetterberg, H., Blennow, K., Zetterberg, M., Shareef, F., Siegel, N. H., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12972157
Additional file 3 of Neurofilament light chain in the vitreous humor of the eye
Subramanian, M. L., Vig, V., Chung, J., Fiorello, M. G., Xia, W., Zetterberg, H., Blennow, K., Zetterberg, M., Shareef, F., Siegel, N. H., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12972151
Additional file 6 of Neurofilament light chain in the vitreous humor of the eye
Subramanian, M. L., Vig, V., Chung, J., Fiorello, M. G., Xia, W., Zetterberg, H., Blennow, K., Zetterberg, M., Shareef, F., Siegel, N. H., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12972160
- Authors
- Tripathy, D., Thirumangalakudi, L., & Grammas, P.
- Affiliations
- Texas Tech University (US)
- Corresponding author
- Grammas, Paula
- ORCID
- Grammas, Paula
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2007-07-06
- Volume
- 11
- Issue
- 4
- Pages
- 447-455
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1463939286
- Cited by
- 51
- References
- 0
- Citations by year
- 2025: 1 · 2024: 7 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 7 · 2019: 2 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 1
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG 15964, AG-020569, R01AG020569, R01AG015964)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- macrophage inflammatory protein-1alpha, Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Animals, Brain, Cells, Cultured, Endothelium, Vascular, Gene Expression Regulation, Humans, Microcirculation, RNA, Messenger, Lipid Peroxidation, Up-Regulation, Oxidative Stress, Reverse Transcriptase Polymerase Chain Reaction, Rats, Chemokine CCL3
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