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Innate Immune System Activation and Neuroinflammation in Down Syndrome and Neurodegeneration: Therapeutic Targets or Partners?

Overview
Specialty Geriatrics
Date 2021 Oct 4
PMID 34603007
Citations 12
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Abstract

Innate immune system activation and inflammation are associated with and may contribute to clinical outcomes in people with Down syndrome (DS), neurodegenerative diseases such as Alzheimer's disease (AD), and normal aging. In addition to serving as potential diagnostic biomarkers, innate immune system activation and inflammation may play a contributing or causal role in these conditions, leading to the hypothesis that effective therapies should seek to dampen their effects. However, recent intervention studies with the innate immune system activator granulocyte-macrophage colony-stimulating factor (GM-CSF) in animal models of DS, AD, and normal aging, and in an AD clinical trial suggest that activating the innate immune system and inflammation may instead be therapeutic. We consider evidence that DS, AD, and normal aging are accompanied by innate immune system activation and inflammation and discuss whether and when during the disease process it may be therapeutically beneficial to suppress or promote such activation.

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References
1.
Sanan D, Weisgraber K, Russell S, Mahley R, Huang D, Saunders A . Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3. J Clin Invest. 1994; 94(2):860-9. PMC: 296168. DOI: 10.1172/JCI117407. View

2.
Kong T, Choi J, Park H, Choi B, Snyder B, Bukhari S . Reduction in programmed cell death and improvement in functional outcome of transient focal cerebral ischemia after administration of granulocyte-macrophage colony-stimulating factor in rats. Laboratory investigation. J Neurosurg. 2009; 111(1):155-63. DOI: 10.3171/2008.12.JNS08172. View

3.
Wisniewski T, Golabek A, Matsubara E, Ghiso J, Frangione B . Apolipoprotein E: binding to soluble Alzheimer's beta-amyloid. Biochem Biophys Res Commun. 1993; 192(2):359-65. DOI: 10.1006/bbrc.1993.1423. View

4.
Lambert J, Ibrahim-Verbaas C, Harold D, Naj A, Sims R, Bellenguez C . Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat Genet. 2013; 45(12):1452-8. PMC: 3896259. DOI: 10.1038/ng.2802. View

5.
Galimberti D, Fenoglio C, Lovati C, Venturelli E, Guidi I, Corra B . Serum MCP-1 levels are increased in mild cognitive impairment and mild Alzheimer's disease. Neurobiol Aging. 2005; 27(12):1763-8. DOI: 10.1016/j.neurobiolaging.2005.10.007. View