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Chapter 9 - The Effect of Systemic Inflammation on Cognitive Function and Neurodegenerative Disease

Published online by Cambridge University Press:  02 September 2021

By
Colm Cunningham  and
Donal T. Skelly
Edited by
Golam Khandaker ,
Neil Harrison ,
Edward Bullmore  and
Robert Dantzer
Golam Khandaker
Affiliation:
University of Cambridge
Neil Harrison
Affiliation:
Cardiff University Brain Research Imaging Centre (CUBRIC)
Edward Bullmore
Affiliation:
University of Cambridge
Robert Dantzer
Affiliation:
University of Texas, MD Anderson Cancer Center
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Summary

Chronic neurodegenerative diseases represent a major challenge for health systems worldwide. The most common diseases are Alzheimer’s disease (AD), Parkinson’s disease (PD), Lewy body dementia, frontotemporal dementia, amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD) and prion diseases. Multiple sclerosis (MS) is classically considered to be an autoimmune disease but increasingly, it is viewed as a degenerative disease (1).

Type
Chapter
Information
Textbook of Immunopsychiatry , pp. 164 - 189
Publisher: Cambridge University Press
Print publication year: 2021

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References

Trapp, BD, Nave, K-A. Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci. 2008 Jun 17;31(1):247–69.Google Scholar
Redmann, M, Darley-Usmar, V, Zhang, J. The role of autophagy, mitophagy and lysosomal functions in modulating bioenergetics and survival in the context of redox and proteotoxic damage: implications for neurodegenerative diseases. Aging Dis. 2016 Mar 15;7(2):150.Google Scholar
Swardfager, W, Lanctt, K, Rothenburg, L, et al. A meta-analysis of cytokines in Alzheimer’s disease. Biol Psychiatry. 2010;68(10):930–41.Google Scholar
Holmes, C, Cunningham, C, Zotova, E, et al. Systemic inflammation and disease progression in alzheimer disease. Neurology. 2009;73(10):768–74.Google Scholar
King, E, Tiernan O’Brien, J, Donaghy, P, et al. Peripheral inflammation in prodromal Alzheimer’s and Lewy body dementias. Journal of Neurology, Neurosurgery and Psychiatry. 2018;89:339–45.Google Scholar
McManus, RM, Heneka, MT. Role of neuroinflammation in neurodegeneration: new insights. Alzheimers Res Ther. 2017;9(1):14.Google Scholar
Dunn, N, Mullee, M, Perry, VH, Holmes, C. Association between dementia and infectious disease. Alzheimer Dis Assoc Disord. 2005;19(2):91–4.CrossRefGoogle ScholarPubMed
Katan, M, Moon, YP, Paik, MC, et al. Infectious burden and cognitive function. Neurology. 2013 Mar 26;80(13):LP1209–15.Google Scholar
Widmann, CN, Heneka, MT. Long-term cerebral consequences of sepsis. Lancet Neurol. 2014 Jun 1;13(6):630–6.Google Scholar
Zrzavy, T, Höftberger, R, Berger, T, et al. Pro-inflammatory activation of microglia in the brain of patients with sepsis. Neuropathol Appl Neurobiol. 2019 April;45(3):278–90.Google Scholar
Kumar, DKV, Choi, SH, Washicosky, KJ, et al. Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease. Sci Transl Med. 2016 May 25;8(340):340ra72.Google Scholar
Eimer, WA, Vijaya Kumar, DK, Navalpur Shanmugam, NK, et al. Alzheimer’s disease-associated β-amyloid is rapidly seeded by herpesviridae to protect against brain infection. Neuron. 2018 Jul 11;99(1):56–63.e3.Google Scholar
Rasmussen, LS. Postoperative cognitive dysfunction: Incidence and prevention. Best Pract Res Clin Anaesthesiol. 2006;20(2):315–30.Google Scholar
Nadelson, MR, Sanders, RD, Avidan, MS. Perioperative cognitive trajectory in adults. BJA Br J Anaesth. 2014 Mar 1;112(3):440–51.Google Scholar
Ungprasert, P, Wijarnpreecha, K, Thongprayoon, C. Rheumatoid arthritis and the risk of dementia: a systematic review and meta-analysis. Neurol India. 2016;64(1):56.CrossRefGoogle ScholarPubMed
Chen, C-K, Wu, Y-T, Chang, Y-C. Association between chronic periodontitis and the risk of Alzheimer’s disease: a retrospective, population-based, matched-cohort study. Alzheimers Res Ther. 2017;9(1):56.Google Scholar
Chen, C-K, Wu, Y-T, Chang, Y-C. Periodontal inflammatory disease is associated with the risk of Parkinson’s disease: a population-based retrospective matched-cohort study. Emsley H, editor. PeerJ. 2017;5:e3647.Google Scholar
Ide, M, Harris, M, Stevens, A, et al. Periodontitis and cognitive decline in Alzheimer’s disease. PLoS One. 2016;11(3):e0151081.CrossRefGoogle ScholarPubMed
Yaffe, K, Kanaya, A, Lindquist, K, et al. The metabolic syndrome, inflammation, and risk of cognitive decline. J Am Med Assoc. 2004;292(18):2237–42.Google Scholar
Clegg, A, Young, J, Iliffe, S, Rikkert, MO, Rockwood, K. Frailty in elderly people. Lancet. 2013;381(9868):752–62.Google Scholar
Cunningham, C. Systemic inflammation and delirium: important co-factors in the progression of dementia. Biochem Soc Trans. 2011;39(4):945–53.CrossRefGoogle ScholarPubMed
Cerejeira, J, Firmino, H, Vaz-Serra, A, Mukaetova-Ladinska, EB. The neuroinflammatory hypothesis of delirium. Acta Neuropathol. 2010;119(6):737–54.CrossRefGoogle ScholarPubMed
van Gool, WA, van de Beek, D, Eikelenboom, P. Systemic infection and delirium: when cytokines and acetylcholine collide. Lancet. 2010;375(9716):773–5.Google Scholar
Khan, BA, Zawahiri, M, Campbell, NL, Boustani, MA. Biomarkers for deliriuma – a review. J Am Geriatr Soc. 2011;59(SUPPL. 2):S256–61.Google Scholar
George, J, Bleasdale, S, Singleton, SJ. Causes and prognosis of delirium in elderly patients admitted to a district general hospital. Age Ageing. 1997;26(6):423–7.CrossRefGoogle ScholarPubMed
Chang, YL, Tsai, YF, Lin, PJ, Chen, MC, Liu, CY. Prevalence and risk factors for postoperative delirium in a cardiovascular intensive care unit. AmJCrit Care. 2008;17(6):567–75.Google Scholar
Kat, MG, Vreeswijk, R, De Jonghe, JFM, et al. Long-term cognitive outcome of delirium in elderly hip surgery patients: a prospective matched controlled study over two and a half years. Dement Geriatr Cogn Disord. 2008;26(1):1–8.Google Scholar
Rudolph, JL, Jones, RN, Levkoff, SE, et al. Derivation and validation of a preoperative prediction rule for delirium after cardiac surgery. Circulation. 2009;119(2):229–36.CrossRefGoogle ScholarPubMed
Inouye, SK, Charpentier, PA. Precipitating factors for delirium in hospitalized elderly persons: predictive model and interrelationship with baseline vulnerability. J Am Med Assoc. 1996;275(11):852–7.Google Scholar
Eriksson, I, Gustafson, Y, Fagerstrom, L, Olofsson, B. Urinary tract infection in very old women is associated with delirium. Int Psychogeriatr. 2011;23(3):496–502.Google Scholar
McKenzie, R, Stewart, MT, Bellantoni, MF, Finucane, TE. Bacteriuria in individuals who become delirious. Am J Med. 2014 Apr 1;127(4):255–7.Google Scholar
Davis, DHJ, Skelly, DT, Murray, C, et al. Worsening cognitive impairment and neurodegenerative pathology progressively increase risk for delirium. Am J Geriatr Psychiatry. 2015;23(4):403–15.Google Scholar
Witlox, J, Eurelings, LSM, De Jonghe, JFM, et al. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA. 2010;304(4):443–51.Google Scholar
Saczynski, JS, Marcantonio, ER, Quach, L, et al. Cognitive trajectories after postoperative delirium. N Engl J Med. 2012 Jul 5;367(1):30–9.Google Scholar
Fong, TG, Jones, RN, Shi, P, et al. Delirium accelerates cognitive decline in Alzheimer disease. Neurology. 2009;72(18):1570–5.Google Scholar
Davis, DHJ, Muniz Terrera, G, Keage, H, et al. Delirium is a strong risk factor for dementia in the oldest-old: a population-based cohort study. Brain. 2012 Sep 9;135(9):2809–16.CrossRefGoogle Scholar
DJ, D, Muniz-Terrera, G, HD, K, et al. Association of delirium with cognitive decline in late life: a neuropathologic study of 3 population-based cohort studies. JAMA Psychiatry. 2017 Mar 1;74(3):244–51.Google Scholar
Holmes, C, Butchart, J. Systemic inflammation and Alzheimer’s disease. Biochem Soc Trans. 2011 Aug 1;39(4):LP898–901.Google Scholar
Brugger, F, Erro, R, Balint, B, et al. Why is there motor deterioration in Parkinson’s disease during systemic infections – a hypothetical view. npj Park Dis. 2015;1(1):15014.Google Scholar
Correale, J, Fiol, M, Gilmore, W. The risk of relapses in multiple sclerosis during systemic infections. Neurology. 2006 Aug 22;67(4):LP652–9.Google Scholar
Buljevac, D, Flach, HZ, Hop, WCJ, et al. Prospective study on the relationship between infections and multiple sclerosis exacerbations. Brain. 2002 May 1;125(5):952–60.Google Scholar
Smith, KJ, McDonald, WI. The pathophysiology of multiple sclerosis: the mechanisms underlying the production of symptoms and the natural history of the disease. Philos Trans R Soc London Ser B Biol Sci. 1999 Oct 29;354(1390):LP1649–73.CrossRefGoogle ScholarPubMed
DM, W, Rodriguez, M. Premenstrual multiple sclerosis pseudoexacerbations: role of body temperature and prevention with aspirin. Arch Neurol. 2006 Jul 1;63(7):1005–8.Google Scholar
Moreau, T, Coles, A, Wing, M, et al. Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis. Brain. 1996;119(1):225–37.CrossRefGoogle ScholarPubMed
Shimabukuro-Vornhagen, A, Gödel, P, Subklewe, M, et al. Cytokine release syndrome. J Immunother Cancer. 2018;6(1):56.Google Scholar
Dantzer, R, O’Connor, JC, Freund, GG, Johnson, RW, Kelley, KW. From inflammation to sickness and depression: When the immune system subjugates the brain. Nat Rev Neurosci. 2008;9(1):46–56.Google Scholar
Matsumura, K, Kaihatsu, S, Imai, H, et al. Cyclooxygenase in the vagal afferents: is it involved in the brain prostaglandin response evoked by lipopolysaccharide? Auton Neurosci Basic Clin. 2000;85(1–3):88–92.Google Scholar
Hosoi, T, Okuma, Y, Matsuda, T, Nomura, Y. Novel pathway for LPS-induced afferent vagus nerve activation: possible role of nodose ganglion. Auton Neurosci Basic Clin. 2005;120(1–2):104–7.Google Scholar
Chakravarty, S. Toll-like receptor 4 on nonhematopoietic cells sustains CNS inflammation during endotoxemia, independent of systemic cytokines. J Neurosci. 2005;25(7):1788–96.CrossRefGoogle ScholarPubMed
Gosselin, D, Rivest, S. MyD88 signaling in brain endothelial cells is essential for the neuronal activity and glucocorticoid release during systemic inflammation. Mol Psychiatry. 2008;13(5):480–97.CrossRefGoogle ScholarPubMed
Murray, CL, Skelly, DT, Cunningham, C. Exacerbation of CNS inflammation and neurodegeneration by systemic LPS treatment is independent of circulating IL-1β and IL-6. J Neuroinflammation. 2011 May 17;8:50.Google Scholar
Saper, CB, Romanovsky, AA, Scammell, TE. Neural circuitry engaged by prostaglandins during the sickness syndrome. Nat Neurosci. 2012 Jul 26;15:1088.Google Scholar
Quan, N, Stern, EL, Whiteside, MB, Herkenham, M. Induction of pro-inflammatory cytokine mRNAs in the brain after peripheral injection of subseptic doses of lipopolysaccharide in the rat. J Neuroimmunol. 1999 Jan 1;93(1–2):72–80.CrossRefGoogle ScholarPubMed
Gutierrez, EG, Banks, WA, Kastin, AJ. Murine tumor necrosis factor alpha is transported from blood to brain in the mouse. J Neuroimmunol. 1993;47(2):169–76.Google Scholar
Banks, WA, Kastin, AJ. Blood to brain transport of interleukin links the immune and central nervous systems. Life Sci. 1991;48(25):PL117–21.Google Scholar
Varatharaj, A, Galea, I. The blood-brain barrier in systemic inflammation. Brain Behav Immun. 2017;60:1–12.CrossRefGoogle ScholarPubMed
Zlokovic, B. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008;57(2):178–201.Google Scholar
Balusu, S, Van Wonterghem, E, De Rycke, R, et al. Identification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus‐derived extracellular vesicles. EMBO Mol Med. 2016 Oct 8;10:1162–83.Google Scholar
Erny, D, de Angelis, ALH, Jaitin, D, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015 Jul 1;18(7):965–77.Google Scholar
Rothhammer, V, Borucki, DM, Tjon, EC, et al. Microglial control of astrocytes in response to microbial metabolites. Nature. 2018;557(7707):724–8.Google Scholar
Itagaki, S, McGeer, PL, Akiyama, H, Zhu, S, Selkoe, D. Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease. J Neuroimmunol. 1989;24(3):173–82.CrossRefGoogle ScholarPubMed
Harold, D, Abraham, R, Hollingworth, P, et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat Genet. 2009;41(10):1088–93.Google Scholar
Hollingworth, P, Sims, R, Gerrish, A, et al. ABCA7 and BIN1 are susceptibility genes for Alzheimer’s disease. Nat Genet. 2011;43:429–35.Google Scholar
Lambert, JC, Ibrahim-Verbaas, CA, Harold, D, et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet. 2013;45(12):1452–8.CrossRefGoogle ScholarPubMed
Shi, H, Belbin, O, Medway, C, et al. Genetic variants influencing human aging from late-onset Alzheimer’s disease (LOAD) genome-wide association studies (GWAS). Neurobiol Aging. 2012 Aug 23;33(8):1849.e5–1849.18.Google Scholar
Jonsson, T, Stefansson, H, Steinberg, S, et al. Variant of TREM2 associated with the risk of Alzheimer’s disease. N Engl J Med. 2013 Nov 14;368(2):107–16.Google Scholar
Guerreiro, R, Wojtas, A, Bras, J, et al. TREM2 variants in Alzheimer’s disease. N Engl J Med. 2013 Nov 14;368(2):117–27.Google Scholar
Combrinck, MI, Perry, VH, Cunningham, C. Peripheral infection evokes exaggerated sickness behaviour in pre-clinical murine prion disease. Neuroscience. 2002;112(1):7–11.Google Scholar
Cunningham, C. Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration. J Neurosci. 2005;25(40):9275–84.CrossRefGoogle ScholarPubMed
Perry, VH, Cunningham, C, Holmes, C. Systemic infections and inflammation affect chronic neurodegeneration. Nat Rev Immunol. 2007;7(2):161–7.CrossRefGoogle ScholarPubMed
Murray, C, Sanderson, DJ, Barkus, C, et al. Systemic inflammation induces acute working memory deficits in the primed brain: Relevance for delirium. Neurobiol Aging. 2012;33(3):603–16.Google Scholar
Godbout, JP. Exaggerated neuroinflammation and sickness behavior in aged mice after activation of the peripheral innate immune system. FASEB J. 2005;19(10):1329–31.Google Scholar
Frank, MG, Barrientos, RM, Watkins, LR, Maier, SF. Aging sensitizes rapidly isolated hippocampal microglia to LPS ex vivo. J Neuroimmunol. 2010 Sep 14;226(1):181–4.CrossRefGoogle ScholarPubMed
Pace, JL, Russell, SW, Torres, BA, Johnson, HM, Gray, PW. Recombinant mouse gamma interferon induces the priming step in macrophage activation for tumor cell killing. J Immunol. 1983;130(5):2011–3.CrossRefGoogle ScholarPubMed
Walsh, DT, Betmouni, S, Perry, VH. Absence of detectable IL-1β production in Murine Prion disease: a model of chronic neurodegeneration. J Neuropathol Exp Neurol. 2001 Feb 1;60(2):173–82.Google Scholar
Holtman, IR, Raj, DD, Miller, JA, et al. Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: a co-expression meta-analysis. Acta Neuropathol Commun. 2015;3(1):31.Google Scholar
Mathys, H, Adaikkan, C, Gao, F, et al. Temporal tracking of microglia activation in neurodegeneration at single-cell resolution article temporal tracking of microglia activation in neurodegeneration at single-cell resolution. Cell Rep. 2017;21(2):366–80.Google Scholar
Keren-Shaul, H, Spinrad, A, Weiner, A, et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell. 2017 Jun 15;169(7):1276–90.e17.Google Scholar
Mrdjen, D, Pavlovic, A, Hartmann, FJ, et al. High-dimensional single-cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health, aging, and disease. Immunity. 2018 Feb 20;48(2):380–95.e6.Google Scholar
Deczkowska, A, Keren-Shaul, H, Weiner, A, et al. Disease-associated microglia: a universal immune sensor of neurodegeneration. Cell. 2018;173(5):1073–81.Google Scholar
Hughes, MM, Field, RH, Perry, VH Microglia in the degenerating brain are capable of phagocytosis of beads and of apoptotic cells, but do not efficiently remove PrPSc, even upon LPS stimulation. Glia. 2010 Sep 27;58(16):2017–30.Google Scholar
Cunningham, C. Microglia and neurodegeneration: the role of systemic inflammation. Glia. 2013;61(1):71–90.Google Scholar
Field, R, Campion, S, Warren, C, Murray, C, Cunningham, C. Systemic challenge with the TLR3 agonist poly I:C induces amplified IFNα/β and IL-1β responses in the diseased brain and exacerbates chronic neurodegeneration. Brain Behav Immun. 2010;24(6):996–1007.CrossRefGoogle ScholarPubMed
Yin, Z, Raj, D, Saiepour, N, et al. Immune hyperreactivity of Aβ plaque-associated microglia in Alzheimer’s disease. Neurobiol Aging. 2017;55:115–22.Google Scholar
Lopez-Rodriguez, AB, Hennessy, E, Murray, C, et al. Microglial and Astrocyte priming in the APP/PS1 model of Alzheimer’s Disease: increased vulnerability to acute inflammation and cognitive deficits. bioRxiv. 2018 Jan 1;344218.Google Scholar
Kyrkanides, S, Tallents, RH, Miller, JNH, et al. Osteoarthritis accelerates and exacerbates Alzheimer’s disease pathology in mice. J Neuroinflammation. 2011;8(1):112.Google Scholar
Godoy, MCP, Tarelli, R, Ferrari, CC, Sarchi, MI, Pitossi, FJ. Central and systemic IL-1 exacerbates neurodegeneration and motor symptoms in a model of Parkinson’s disease. Brain. 2008;131(7):1880–94.Google Scholar
Palin, K, Cunningham, C, Forse, P, Perry, VH, Platt, N. Systemic inflammation switches the inflammatory cytokine profile in CNS Wallerian degeneration. Neurobiol Dis. 2008;30(1):19–29.Google Scholar
Cunningham, C. Microglia and neurodegeneration. The role of systemic inflammation. Glia. 2013;61(1):71–90.Google Scholar
Saijo, K, Glass, CK. Microglial cell origin and phenotypes in health and disease. Nat Rev Immunol. 2011 Oct 25;11(11):775–87.Google Scholar
Couch, Y, Alvarez-Erviti, L, Sibson, NR, Wood, MJA, Anthony, DC. The acute inflammatory response to intranigral α-synuclein differs significantly from intranigral lipopolysaccharide and is exacerbated by peripheral inflammation. J Neuroinflammation. 2011 Nov 28;8:166.Google Scholar
Andersson, U, Tracey, KJ. HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol. 2011;29:139–62.Google Scholar
Paudel, YN, Shaikh, MF, Chakraborti, A, et al. HMGB1: a common biomarker and potential target for TBI, neuroinflammation, epilepsy, and cognitive dysfunction. Front Neurosci. 2018 Sep 11;12:628.Google Scholar
Fonken, LK, Frank, MG, Kitt, MM, et al. The alarmin HMGB1 mediates age-induced neuroinflammatory priming. J Neurosci. 2016 Jul 27;36(30):LP7946–56.CrossRefGoogle ScholarPubMed
Weber, MD, Frank, MG, Tracey, KJ, Watkins, LR, Maier, SF. Stress induces the danger-associated molecular pattern HMGB-1 in the hippocampus of male sprague dawley rats: a priming stimulus of microglia and the NLRP3 inflammasome. J Neurosci. 2015 Jan 7;35(1):316–24.Google Scholar
Barrientos, RM, Frank, MG, Hein, AM, et al. Time course of hippocampal IL-1 β and memory consolidation impairments in aging rats following peripheral infection. Brain Behav Immun. 2009;23(1):46–54.Google Scholar
Hong, S, Beja-Glasser, VF, Nfonoyim, BM, et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science. 2016 May 6;352(6286):712–6.Google Scholar
Ramaglia, V, Hughes, TR, Donev, RM, et al. C3-dependent mechanism of microglial priming relevant to multiple sclerosis. Proc Natl Acad Sci USA. 2012 Jan 17;109(3):965–70.Google Scholar
Raj, DDA, Jaarsma, D, Holtman, IR, et al. Priming of microglia in a DNA-repair deficient model of accelerated aging. Neurobiol Aging. 2014;35(9):2147–60.CrossRefGoogle Scholar
Lunnon, K, Teeling, JL, Tutt, AL, et al. Systemic inflammation modulates Fc receptor expression on microglia during chronic neurodegeneration. J Immunol. 2011 Jun 15;186(12):7215–24.Google Scholar
Poliani, PL, Wang, Y, Fontana, E, et al. TREM2 sustains microglial expansion during aging and response to demyelination. J Clin Invest. 2015 May 1;125(5):2161–70.Google Scholar
Lill, CM, Rengmark, A, Pihlstrøm, L, et al. The role of TREM2 R47H as a risk factor for Alzheimer’s disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson’s disease. Alzheimer’s Dement. 2015 Dec 1;11(12):1407–16.Google Scholar
Zhao, Y, Wu, X, Li, X, et al. TREM2 is a receptor for β-amyloid that mediates microglial function. Neuron. 2018 Mar 7;97(5):1023–31.e7.CrossRefGoogle ScholarPubMed
Fahrenhold, M, Rakic, S, Classey, J, et al. TREM2 expression in the human brain: a marker of monocyte recruitment? Brain Pathol. 2018 Sep;28(5):595–602.Google Scholar
Vitek, MP, Brown, CM, Colton, CA. APOE genotype-specific differences in the innate immune response. Neurobiol Aging. 2009 Sep;30(9):1350–60.Google Scholar
Gale, SC, Gao, L, Mikacenic, C, et al. APOε4 is associated with enhanced in vivo innate immune responses in human subjects. J Allergy Clin Immunol. 2014 Jul;134(1):127–34.Google Scholar
Bennett, FC, Bennett, ML, Yaqoob, F, et al. A combination of ontogeny and CNS environment establishes microglial identity. Neuron. 2018 Jun 27;98(6):1170–83e8.Google Scholar
Costello, DA, Lyons, A, Denieffe, S, et al. Long term potentiation is impaired in membrane glycoprotein CD200-deficient mice: a role for Toll-like receptor activation. J Biol Chem. 2011 Oct 7;286(40):34722–32.Google Scholar
Wynne, AM, Henry, CJ, Huang, Y, Cleland, A, Godbout, JP. Protracted downregulation of CX3CR1 on microglia of aged mice after lipopolysaccharide challenge. Brain Behav Immun. 2010;24(7):1190–201.Google Scholar
Lehrman, EK, Wilton, DK, Litvina, EY, et al. CD47 protects synapses from excess microglia-mediated pruning during development. Neuron. 2018;100(1):120–134.e6.CrossRefGoogle ScholarPubMed
O’Sullivan, JB, Ryan, KM, Curtin, NM, Harkin, A, Connor, TJ. Noradrenaline reuptake inhibitors limit neuroinflammation in rat cortex following a systemic inflammatory challenge: implications for depression and neurodegeneration. Int J Neuropsychopharmacol. 2009 Jun 1;12(5):687–99.Google Scholar
Heneka, MT, Nadrigny, F, Regen, T, et al. Locus ceruleus controls Alzheimer’s disease pathology by modulating microglial functions through norepinephrine. Proc Natl Acad Sci USA. 2010 Mar 30;107(13):6058–63.Google Scholar
Tracey, KJ. Reflex control of immunity. Nat Rev Immunol. 2009;9(6):418–28.Google Scholar
Frank, MG, Thompson, BM, Watkins, LR, Maier, SF. Glucocorticoids mediate stress-induced priming of microglial pro-inflammatory responses. Brain Behav Immun. 2012 Feb 24;26(2):337–45.CrossRefGoogle ScholarPubMed
Ros-Bernal, F, Hunot, S, Herrero, MT, et al. Microglial glucocorticoid receptors play a pivotal role in regulating dopaminergic neurodegeneration in parkinsonism. Proc Natl Acad Sci. 2011 Apr 19;108(16): 6632–37.CrossRefGoogle ScholarPubMed
Munhoz, CD, Sorrells, SF, Caso, JR, Scavone, C, Sapolsky, RM. Glucocorticoids exacerbate lipopolysaccharide-induced signaling in the frontal cortex and hippocampus in a dose-dependent manner. J Neurosci. 2010;30(41):13690–8.Google Scholar
Drake, C, Boutin, H, Jones, MS, et al. Brain inflammation is induced by co-morbidities and risk factors for stroke. Brain Behav Immun. 2011 Aug 16;25(6–4):1113–22.Google Scholar
Sheng, JG, Bora, SH, Xu, G, et al. Lipopolysaccharide-induced-neuroinflammation increases intracellular accumulation of amyloid precursor protein and amyloid β peptide in APPswe transgenic mice. Neurobiol Dis. 2003;14(1):133–45.Google Scholar
Cunningham, C, Hennessy, E. Co-morbidity and systemic inflammation as drivers of cognitive decline: new experimental models adopting a broader paradigm in dementia research. Alzheimer’s Res Ther. 2015;7(1):33.Google Scholar
Muccigrosso, MM, Ford, J, Benner, B, et al. Cognitive deficits develop 1 month after diffuse brain injury and are exaggerated by microglia-associated reactivity to peripheral immune challenge. Brain Behav Immun. 2016 May 14;54:95–109.Google Scholar
Johnson, VE, Stewart, JE, Begbie, FD, et al. Inflammation and white matter degeneration persist for years after a single traumatic brain injury. Brain. 2013 Jan 1;136(1):28–42.CrossRefGoogle ScholarPubMed
Netea, MG, Latz, E, Mills, KHG, O’Neill, LAJ. Innate immune memory: a paradigm shift in understanding host defense. Nat Immunol. 2015 Jun 18;16(7):675–9.Google Scholar
Püntener, U, Booth, SG, Perry, VH, Teeling, JL. Long-term impact of systemic bacterial infection on the cerebral vasculature and microglia. J Neuroinflammation. 2012 Jun 27;9:146.Google Scholar
Wendeln, A-C, Degenhardt, K, Kaurani, L, et al. Innate immune memory in the brain shapes neurological disease hallmarks. Nature. 2018;556(7701):332–8.Google Scholar
Bodea, L-G, Wang, Y, Linnartz-Gerlach, B, et al. Neurodegeneration by activation of the microglial complement–phagosome pathway. J Neurosci. 2014 Jun 18;34(25):LP8546–56.Google Scholar
Askew, K, Li, K, Olmos-alonso, A, et al. Coupled proliferation and apoptosis maintain the rapid turnover of microglia in the adult brain. Cell Rep. 2017;18(2):391–405.Google Scholar
Füger, P, Hefendehl, JK, Veeraraghavalu, K, et al. Microglia turnover with aging and in an Alzheimer’s model via long-term in vivo single-cell imaging. Nat Neurosci. 2017 Aug 28;20(10):1371–6.Google Scholar
Hopperton, KE, Mohammad, D, Trépanier, MO, Giuliano, V, Bazinet, RP. Markers of microglia in post-mortem brain samples from patients with Alzheimer’s disease: a systematic review. Mol Psychiatry. 2017 Dec 12;23:177.Google Scholar
Minett, T, Classey, J, Matthews, FE, et al. Microglial immunophenotype in dementia with Alzheimer’s pathology. J Neuroinflammation. 2016;13(1):135.Google Scholar
Griffin, WST, Sheng, JG, Roberts, GW, Mrak, RE. Interleukin-1 expression in different plaque types in Alzheimer’s disease: significance in plaque evolution. J Neuropathol Exp Neurol. 1995 Mar 1;54(2):276–81.Google Scholar
McGeer, PL, Akiyama, H, Itagaki, S, McGeer, EG. Activation of the classical complement pathway in brain tissue of Alzheimer patients. Neurosci Lett. 1989;107(1):341–6.Google Scholar
Lemstra, AW, Groen in’t Woud, JCM, Hoozemans, JJM, et al. Microglia activation in sepsis: a case-control study. J Neuroinflammation. 2007;4(1):4.Google Scholar
Gosselin, D, Skola, D, Coufal, NG, et al. An environment-dependent transcriptional network specifies human microglia identity. Science. 2017 Jun 23;356(6344):eaal3222.Google Scholar
Galatro, TF, Holtman, IR, Lerario, AM, et al. Transcriptomic analysis of purified human cortical microglia reveals age-associated changes. Nat Neurosci. 2017;20(8):1162–71.Google Scholar
Pugh, CR, Kumagawa, K, Fleshner, M, et al. Selective effects of peripheral lipopolysaccharide administration on contextual and auditory-cue fear conditioning. Brain Behav Immun. 1998;12(3):212–29.Google Scholar
Katsuki, H, Nakai, S, Hirai, Y, et al. Interleukin-1β inhibits long-term potentiation in the CA3 region of mouse hippocampal slices. Eur J Pharmacol. 1990;181(3):323–6.Google Scholar
Lynch, MA. Long-term potentiation and memory. Physiol Rev. 2004 Jan 1;84(1):87–136.Google Scholar
Frank, MG, Barrientos, RM, Hein, AM, et al. IL-1RA blocks E. coli-induced suppression of Arc and long-term memory in aged F344 × BN F1 rats. Brain Behav Immun. 2010;24(2):254–62.Google Scholar
Cibelli, M, Fidalgo, AR, Terrando, N, et al. Role of interleukin-1β in postoperative cognitive dysfunction. Ann Neurol. 2010;68(3):360–8.Google Scholar
Griffin, EW, Skelly, DT, Murray, CL, Cunningham, C. Cyclooxygenase-1-dependent prostaglandins mediate susceptibility to systemic inflammation-induced acute cognitive dysfunction. J Neurosci. 2013;33(38):15248–58.Google Scholar
Skelly, D, Griffin, EW, Murray, C, et al. Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms. Mol Psychiatry. 2019;24:1533–48.Google Scholar
Thygesen, C, Ilkjær, L, Kempf, SJ, et al. Diverse protein profiles in CNS myeloid cells and CNS tissue from lipopolysaccharide- and vehicle-injected APPSWE/PS1ΔE9 transgenic mice implicate cathepsin Z in Alzheimer’s disease. Frontiers in Cellular Neuroscience. 2018; 12:397.Google Scholar
Bhaskar, K, Konerth, M, Kokiko-Cochran, ON, et al. Regulation of tau pathology by the microglial fractalkine receptor. Neuron. 2010 Oct 6;68(1):19–31.Google Scholar
Gao, H-M, Zhang, F, Zhou, H, et al. Neuroinflammation and α-synuclein dysfunction potentiate each other, driving chronic progression of neurodegeneration in a mouse model of Parkinson’s disease. Environ Health Perspect. 2011 Jun 18;119(6):807–14.Google Scholar
Moreno, B, Jukes, JP, Vergara-Irigaray, N, et al. Systemic inflammation induces axon injury during brain inflammation. Ann Neurol. 2011;70(6):932–42.Google Scholar
Sofroniew, MV. Astrocyte barriers to neurotoxic inflammation. Nat Rev Neurosci. 2015 Apr 20;16(5):249–63.Google Scholar
Murray, KN, Parry-Jones, AR, Allan, SM. Interleukin-1 and acute brain injury. Frontiers in Cellular Neuroscience. 2015;9:18.Google Scholar
Wang, Y, Jin, S, Sonobe, Y, et al. Interleukin-1β induces blood–brain barrier disruption by downregulating sonic hedgehog in astrocytes. PLoS One. 2014 Oct 14;9(10):e110024.Google Scholar
Watanabe, M, Masaki, K, Yamasaki, R, et al. Th1 cells downregulate connexin 43 gap junctions in astrocytes via microglial activation. Sci Rep. 2016 Dec 8;6:38387.Google Scholar
D’Mello, C, Le, T, Swain, MG. Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factor signaling during peripheral organ inflammation. J Neurosci. 2009 Feb 18;29(7):2089–102.Google Scholar
Vacas, S, Degos, V, Tracey, KJ, Maze, M. High-mobility group box 1 protein initiates postoperative cognitive decline by engaging bone marrow–derived macrophages. Anesthesiology. 2014 May 1;120(5):1160–7.Google Scholar
Andonegui, G, Zelinski, EL, Schubert, CL, et al. Targeting inflammatory monocytes in sepsis-associated encephalopathy and long-term cognitive impairment. JCI Insight. 2018 May 3;3(9):e99364.Google Scholar
Waltl, I, Käufer, C, Bröer, S, et al. Macrophage depletion by liposome-encapsulated clodronate suppresses seizures but not hippocampal damage after acute viral encephalitis. Neurobiol Dis. 2018;110:192–205.Google Scholar
Garré, JM, Silva, HM, Lafaille, JJ, Yang, G. CX3CR1+ monocytes modulate learning and learning-dependent dendritic spine remodeling via TNF-α. Nat Med. 2017 May 15;23:714.Google Scholar
McColl, BW, Rothwell, NJ, Allan, SM. Systemic inflammatory stimulus potentiates the acute phase and CXC chemokine responses to experimental stroke and exacerbates brain damage via interleukin-1- and neutrophil-dependent mechanisms. J Neurosci. 2007;27(16):4403–12.Google Scholar
Blank, T, Detje, CN, Spieß, A, et al. Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment. Immunity. 2016;44(4):901–912.Google Scholar
Le Thuc, O, Cansell, C, Bourourou, M, et al. Central CCL2 signaling onto MCH neurons mediates metabolic and behavioral adaptation to inflammation. EMBO Rep. 2016 Dec 1;17(12):LP1738–52.Google Scholar
Marciniak, E, Faivre, E, Dutar, P, et al. The chemokine MIP-1α/CCL3 impairs mouse hippocampal synaptic transmission, plasticity and memory. Sci Rep. 2015 Oct 29;5:15862.Google Scholar
Hasegawa-Ishii, S, Inaba, M, Umegaki, H, et al. Endotoxemia-induced cytokine-mediated responses of hippocampal astrocytes transmitted by cells of the brain–immune interface. Sci Rep. 2016 May 5;6:25457.Google Scholar
Villeda, SA, Luo, J, Mosher, KI, et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 2011 Aug 31;477(7362):90–6.Google Scholar
Kreisl, WC, Lyoo, CH, McGwier, M, et al. In vivo radioligand binding to translocator protein correlates with severity of Alzheimer’s disease. Brain. 2013 Jul 1;136(7):2228–38.Google Scholar
Sandiego, CM, Gallezot, J-D, Pittman, B, et al. Imaging robust microglial activation after lipopolysaccharide administration in humans with PET. Proc Natl Acad Sci. 2015 Oct 6;112(40):LP12468LP–73.Google Scholar
Owen, DR, Narayan, N, Wells, L, et al. Pro-inflammatory activation of primary microglia and macrophages increases 18 kDa translocator protein expression in rodents but not humans. J Cereb Blood Flow Metab. 2017 May 22;37(8):2679–90.Google Scholar
Notter, T, Coughlin, JM, Sawa, A, Meyer, U. Reconceptualization of translocator protein as a biomarker of neuroinflammation in psychiatry. Mol Psychiatry. 2017 Dec 5;23:36.Google Scholar
Tronel, C, Largeau, B, Santiago Ribeiro, MJ, Guilloteau, D, Dupont A-C, Arlicot N. Molecular targets for PET imaging of activated microglia: the current situation and future expectations. Int J Mol Sci. 2017 Apr 11;18(4):802.Google Scholar
Horti, AG, Naik, R, Foss, CA, et al. PET imaging of microglia by targeting macrophage colony-stimulating factor 1 receptor (CSF1R). Proc Natl Acad Sci. 2019 Jan 11;201812155.Google Scholar
Harrison, NA, Brydon, L, Walker, C, et al. Neural origins of human sickness in interoceptive responses to inflammation. Biol Psychiatry. 2009 Sep 1;66(5):415–22.Google Scholar
Harrison, NA, Cooper, E, Dowell, NG, et al. Quantitative magnetization transfer imaging as a biomarker for effects of systemic inflammation on the brain. Biol Psychiatry. 2015 Jul 1;78(1):49–57.Google Scholar
Guldbrandsen, A, Vethe, H, Farag, Y, et al. In-depth characterization of the cerebrospinal fluid (CSF) proteome displayed through the CSF proteome resource (CSF-PR). Mol Cell Proteomics. 2014 Nov;13(11):3152–63.Google Scholar
Guldbrandsen, A, Farag, Y, Kroksveen, AC, et al. CSF-PR 2.0: an interactive literature guide to quantitative cerebrospinal fluid mass spectrometry data from neurodegenerative disorders. Mol & Cell Proteomics. 2017 Feb 1;16(2):LP300–9.Google Scholar
Cape, E, Hall, RJ, van Munster, BC, et al. Cerebrospinal fluid markers of neuroinflammation in delirium: a role for interleukin-1β in delirium after hip fracture. J Psychosom Res. 2014;77(3):219–25.Google Scholar
MacLullich, AMJ, Edelshain, BT, Hall, RJ, et al. Cerebrospinal fluid interleukin-8 levels are higher in people with hip fracture with perioperative delirium than in controls. J Am Geriatr Soc. 2011;59(6):1151–3.Google Scholar
Lind, A-L, Wu, D, Freyhult, E, et al. A multiplex protein panel applied to cerebrospinal fluid reveals three new biomarker candidates in ALS but none in neuropathic pain patients. PLoS One. 2016 Feb 25;11(2):e0149821.Google Scholar
Coutinho, LG, Grandgirard, D, Leib, SL, Agnez-Lima, LF. Cerebrospinal-fluid cytokine and chemokine profile in patients with pneumococcal and meningococcal meningitis. BMC Infect Dis. 2013;13(1):326.Google Scholar
Pinheiro, MAL, Kooij, G, Mizee, MR, et al. Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke. Biochim Biophys Acta (BBA)-Molecular Basis Dis. 2016;1862(3):461–71.Google Scholar
Rostami, A, Ciric, B. Role of Th17 cells in the pathogenesis of CNS inflammatory demyelination. J Neurol Sci. 2013;333(1):76–87.Google Scholar
Bielekova, B, Pranzatelli, MR. Promise, progress, and pitfalls in the search for central nervous system biomarkers in neuroimmunological diseases: a role for cerebrospinal fluid immunophenotyping. Semin Pediatr Neurol. 2017;24(3):229–39.Google Scholar
Ajami, B, Samusik, N, Wieghofer, P, et al. Single-cell mass cytometry reveals distinct populations of brain myeloid cells in mouse neuroinflammation and neurodegeneration models. Nat Neurosci. 2018;21(4):541–51.Google Scholar
Todorovic, V. Single-cell RNA-seq – now with protein. Nat Methods. 2017 Oct 31;14:1028.Google Scholar
Blennow, K, Hampel, H, Weiner, M, Zetterberg, H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol. 2010 Feb 16;6:131.Google Scholar
Blennow, K, Zetterberg, H. Biomarkers for Alzheimer’s disease: current status and prospects for the future. J Intern Med. 2018 Dec;284(6):643–63.Google Scholar
Felger, JC, Haroon, E, Patel, TA, et al. What does plasma CRP tell us about peripheral and central inflammation in depression? Mol Psychiatry. 2020; Jun;25(6):1301–1311.Google Scholar
Han, S, Lin, YC, Wu, T, et al. Comprehensive immunophenotyping of cerebrospinal fluid cells in patients with neuroimmunological diseases. J Immunol. 2014 Mar 15;192(6):2551–63.Google Scholar
Franceschi, C, Capri, M, Monti, D, et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev. 2007;128(1):92–105.Google Scholar
Björkqvist, M, Wild, EJ, Thiele, J, et al. A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington’s disease. J Exp Med. 2008 Aug 4;205(8):LP1869–77.Google Scholar
McGeer, PL, Schulzer, M, McGeer, EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology. 1996;47(2):425–32.Google Scholar
Koychev, I, Galna, B, Zetterberg, H, et al. Aβ42/Aβ40 and Aβ42/Aβ38 ratios are associated with measures of gait variability and activities of daily living in mild Alzheimer’s disease: a pilot study. J Alzheimer’s Dis. 2018 Sep 25;65(4):1377–83.Google Scholar
Davis, D, Richardson, S, Hornby, J, et al. The delirium and population health informatics cohort study protocol: ascertaining the determinants and outcomes from delirium in a whole population. BMC Geriatr. 2018 Feb 9;18(1):45.Google Scholar
Schmitt, EM, Saczynski, JS, Kosar, CM, et al. The successful aging after elective surgery (SAGES) study: cohort description and data quality procedures. J Am Geriatr Soc. 2015 Dec;63(12):2463–71.Google Scholar
Butchart, J, Brook, L, Hopkins, V, et al. Etanercept in Alzheimer disease: a randomized, placebo-controlled, double-blind, phase 2 trial. Neurology. 2015 May 26;84(21):2161–8.Google Scholar
Clark, IA, Vissel, B. A neurologist’s guide to TNF biology and to the principles behind the therapeutic removal of excess TNF in disease. Neural Plast. 2015;2015:358263.Google Scholar
Nazmi, A, Griffin, EW, Field, RH, et al. Cholinergic signalling in the forebrain controls microglial phenotype and responses to systemic inflammation. bioRxiv. 2021. doi: https://doi.org/10.1101/2021.01.18.427123Google Scholar

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