The Role of Neuroinflammation in Dementias

Current Neurology and Neuroscience Reports

Volumn 15, Issue 4, 2015, Pages

  Pasqualetti, Giuseppe ^a,d   Brooks, David J ^a,b   Edison, Paul ^a,c  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

^b AARHUS UNIVERSITY   (Denmark)

^c CARDIFF UNIVERSITY   (United Kingdom)

^d UNIVERSITY OF PISA   (Italy)

Author keywords

Alzheimer; Dementia; Frontotemporal; Lewy body; Neuroinflammation; Parkinson

Indexed keywords

CELL PROTEIN; N SEC BUTYL 1 (2 CHLOROPHENYL) N METHYL 3 ISOQUINOLINECARBOXAMIDE C 11; TRANSLOCATOR PROTEIN; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; CELL ACTIVATION; CELL ASSAY; CELL FUNCTION; DEMENTIA; DIAGNOSTIC IMAGING; DIFFUSE LEWY BODY DISEASE; DISEASE ASSOCIATION; DISEASE MARKER; FRONTOTEMPORAL DEMENTIA; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENOME ANALYSIS; HUMAN; IMAGE ANALYSIS; MACROGLIA; MENTAL DISEASE; MOLECULAR DYNAMICS; MOLECULAR PATHOLOGY; NERVOUS SYSTEM INFLAMMATION; NEUROIMAGING; NONHUMAN; OUTCOME ASSESSMENT; PARKINSON DISEASE DEMENTIA; PHENOTYPE; POSITRON EMISSION TOMOGRAPHY; PROTEIN DETERMINATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; BRAIN; COMPLICATION; ENCEPHALITIS; PATHOLOGY;

BRAIN; DEMENTIA; ENCEPHALITIS; HUMANS; NEUROIMAGING;

EID: 84923846065     PISSN: 15284042     EISSN: 15346293     Source Type: Journal    
DOI: 10.1007/s11910-015-0531-7     Document Type: Review

References (114)

1. Prince M et al. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013;9(1):63–75. e2.
2. Emre M, Cummings JL, Lane RM. Rivastigmine in dementia associated with Parkinson’s disease and Alzheimer’s disease: similarities and differences. J Alzheimers Dis. 2007;11(4):509–19.
3. Petersen RC et al. Current concepts in mild cognitive impairment. Arch Neurol. 2001;58(12):1985–92.
4. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256(3):183–94.
5. Schapira AH, Jenner P. Etiology and pathogenesis of Parkinson’s disease. Mov Disord. 2011;26(6):1049–55.
6. Iannaccone S et al. In vivo microglia activation in very early dementia with Lewy bodies, comparison with Parkinson’s disease. Parkinsonism Relat Disord. 2013;19(1):47–52.
7. Varnum MM, Ikezu T. The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer’s disease brain. Arch Immunol Ther Exp (Warsz). 2012;60(4):251–66.
8. McGeer PL et al. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology. 1988;38(8):1285–91.
9. Sastre M et al. Inflammatory risk factors and pathologies associated with Alzheimer’s disease. Curr Alzheimer Res. 2011;8(2):132–41.
10. McGeer PL, Itagaki S, McGeer EG. Expression of the histocompatibility glycoprotein HLA-DR in neurological disease. Acta Neuropathol. 1988;76(6):550–7.
11. Imamura K et al. Cytokine production of activated microglia and decrease in neurotrophic factors of neurons in the hippocampus of Lewy body disease brains. Acta Neuropathol. 2005;109(2):141–50.
12. Mrak RE, Griffin WS. Common inflammatory mechanisms in Lewy body disease and Alzheimer disease. J Neuropathol Exp Neurol. 2007;66(8):683–6.
13. Morales I et al. Neuroinflammation in the pathogenesis of Alzheimer’s disease. A rational framework for the search of novel therapeutic approaches. Front Cell Neurosci. 2014;8:112.
14. Heneka MT, O’Banion MK. Inflammatory processes in Alzheimer’s disease. J Neuroimmunol. 2007;184(1–2):69–91.
15. Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci. 2007;10(11):1387–94.
16. Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 1996;19(8):312–8.
17. Liu X et al. Age-dependent neuroinflammatory responses and deficits in long-term potentiation in the hippocampus during systemic inflammation. Neuroscience. 2012;216:133–42.
18. Mills CD et al. M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol. 2000;164(12):6166–73.
19. Cunningham C. Microglia and neurodegeneration: the role of systemic inflammation. Glia. 2013;61(1):71–90. doi:10.1002/glia.22350. This article is an evidence-based review that reported the most significant articles related to role of neuroinflammation and the progression of chronic neurodegenerative disease.
20. Lyman M et al. Neuroinflammation: the role and consequences. Neurosci Res. 2014;79:1–12.
21. Jimenez S et al. Inflammatory response in the hippocampus of PS1M146L/APP751SL mouse model of Alzheimer’s disease: age-dependent switch in the microglial phenotype from alternative to classic. J Neurosci. 2008;28(45):11650–61.
22. Tanaka S et al. Involvement of interleukin-1 in lipopolysaccaride-induced microglial activation and learning and memory deficits. J Neurosci Res. 2011;89(4):506–14.
23. [Abstracts of the 9th Conference on Alzheimer Disease, Kecskemet, Hungary, September 21–23, 2005]. Ideggyogy Sz, 2005. 58(9–10): p. 344–57.
24. Tanaka S et al. Activation of microglia induces symptoms of Parkinson’s disease in wild-type, but not in IL-1 knockout mice. J Neuroinflammation. 2013;10:143.
25. Heneka MT et al. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature. 2013;493(7434):674–8.
26. Langenfurth A et al. Membrane-type 1 metalloproteinase is upregulated in microglia/brain macrophages in neurodegenerative and neuroinflammatory diseases. J Neurosci Res. 2014;92(3):275–86.
27. Cunningham C et al. Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative disease. Biol Psychiatry. 2009;65(4):304–12.
28. Cunningham C et al. Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration. J Neurosci. 2005;25(40):9275–84.
29. Lunnon K et al. Systemic inflammation modulates Fc receptor expression on microglia during chronic neurodegeneration. J Immunol. 2011;186(12):7215–24.
30. Liu B, Hong JS. Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Ther. 2003;304(1):1–7.
31. Dickson DW et al. Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer’s disease. Glia. 1993;7(1):75–83.
32. Barger SW, Harmon AD. Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E. Nature. 1997;388(6645):878–81.
33. DeGiorgio LA et al. Amyloid precursor protein gene disruption attenuates degeneration of substantia nigra compacta neurons following axotomy. Brain Res. 2002;938(1–2):38–44.
34. McGeer PL, McGeer EG. The alpha-synuclein burden hypothesis of Parkinson disease and its relationship to Alzheimer disease. Exp Neurol. 2008;212(2):235–8.
35. Yoshiyama Y et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron. 2007;53(3):337–51.
36. Lue LF et al. Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer’s disease. Am J Pathol. 1999;155(3):853–62.
37. Ferrari CC et al. Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1beta in the substantia nigra. Neurobiol Dis. 2006;24(1):183–93.
38. Wright AL et al. Neuroinflammation and neuronal loss precede Abeta plaque deposition in the hAPP-J20 mouse model of Alzheimer’s disease. PLoS ONE. 2013;8(4):e59586.
39. de Pablos RM et al. Chronic stress enhances microglia activation and exacerbates death of nigral dopaminergic neurons under conditions of inflammation. J Neuroinflammation. 2014;11:34.
40. Griffin EW et al. Cyclooxygenase-1-dependent prostaglandins mediate susceptibility to systemic inflammation-induced acute cognitive dysfunction. J Neurosci. 2013;33(38):15248–58.
41. Hensley K et al. p38 kinase is activated in the Alzheimer’s disease brain. J Neurochem. 1999;72(5):2053–8.
42. Kim SH, Smith CJ, Van Eldik LJ. Importance of MAPK pathways for microglial pro-inflammatory cytokine IL-1 beta production. Neurobiol Aging. 2004;25(4):431–9.
43. Kielian T, Drew PD. Effects of peroxisome proliferator-activated receptor-gamma agonists on central nervous system inflammation. J Neurosci Res. 2003;71(3):315–25.
44. Bassil F, et al. Insulin, IGF-1 and GLP-1 signaling in neurodegenerative disorders: targets for disease modification? Prog Neurobiol. 2014;118:1–18.
45. Vandal M, et al. Insulin reverses the high-fat diet-induced increase in brain Aβ and improves memory in an animal model of Alzheimer disease. Diabetes. 2014;63:4291–301
46. Ghosh S et al. Sustained interleukin-1beta overexpression exacerbates tau pathology despite reduced amyloid burden in an Alzheimer’s mouse model. J Neurosci. 2013;33(11):5053–64.
47. Detrait ER et al. Peripheral administration of an anti-TNF-alpha receptor fusion protein counteracts the amyloid induced elevation of hippocampal TNF-alpha levels and memory deficits in mice. Neurochem Int. 2014;72:10–3.
48. Sun Q et al. Increased plasma TACE activity in subjects with mild cognitive impairment and patients with Alzheimer’s disease. J Alzheimers Dis. 2014;41(3):877–86.
49. Woodling NS et al. Suppression of Alzheimer-associated inflammation by microglial prostaglandin-E2 EP4 receptor signaling. J Neurosci. 2014;34(17):5882–94.
50. Imamura K et al. Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson’s disease brains. Acta Neuropathol. 2003;106(6):518–26.
51. Hirsch EC, Hunot S. Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol. 2009;8(4):382–97.
52. Brochard V et al. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest. 2009;119(1):182–92.
53. Harms AS et al. MHCII is required for alpha-synuclein-induced activation of microglia, CD4 T cell proliferation, and dopaminergic neurodegeneration. J Neurosci. 2013;33(23):9592–600.
54. Lee HJ et al. Direct transfer of alpha-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies. J Biol Chem. 2010;285(12):9262–72.
55. Halliday GM, Stevens CH. Glia: initiators and progressors of pathology in Parkinson’s disease. Mov Disord. 2011;26(1):6–17.
56. Lee HJ, Kim C, Lee SJ. Alpha-synuclein stimulation of astrocytes: potential role for neuroinflammation and neuroprotection. Oxidative Med Cell Longev. 2010;3(4):283–7.
57. He Z et al. Progranulin is a mediator of the wound response. Nat Med. 2003;9(2):225–9.
58. Tang W et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science. 2011;332(6028):478–84.
59. Baker M et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature. 2006;442(7105):916–9.
60. Martens LH et al. Progranulin deficiency promotes neuroinflammation and neuron loss following toxin-induced injury. J Clin Invest. 2012;122(11):3955–9.
61. Bugiani O. FTDP-17: phenotypical heterogeneity within P301S. Ann Neurol. 2000;48(1):126.
62. Bellucci A et al. Presence of reactive microglia and neuroinflammatory mediators in a case of frontotemporal dementia with P301S mutation. Neurodegener Dis. 2011;8(4):221–9.
63. Schmidt R et al. Early inflammation and dementia: a 25-year follow-up of the Honolulu-asia aging study. Ann Neurol. 2002;52(2):168–74.
64. Engelhart MJ et al. Inflammatory proteins in plasma and the risk of dementia: the rotterdam study. Arch Neurol. 2004;61(5):668–72.
65. Jiang T et al. Triggering receptor expressed on myeloid cells 2 knockdown exacerbates aging-related neuroinflammation and cognitive deficiency in senescence-accelerated mouse prone 8 mice. Neurobiol Aging. 2014;35(6):1243–51.
66. Guerreiro R et al. TREM2 variants in Alzheimer’s disease. N Engl J Med. 2013;368(2):117–27.
67. Rayaprolu S et al. TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson’s disease. Mol Neurodegener. 2013;8:19.
68. Rohn TT. The triggering receptor expressed on myeloid cells 2: “TREM-ming” the inflammatory component associated with Alzheimer’s disease. Oxidative Med Cell Longev. 2013;2013:860959.
69. Harold D et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat Genet. 2009;41(10):1088–93.
70. Hollingworth P et al. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat Genet. 2011;43(5):429–35.
71. Hollingworth P et al. Genome-wide association study of Alzheimer’s disease with psychotic symptoms. Mol Psychiatry. 2012;17(12):1316–27.
72. Karch CM et al. Expression of novel Alzheimer’s disease risk genes in control and Alzheimer’s disease brains. PLoS ONE. 2012;7(11):e50976.
73. Wang YL et al. Toll-like receptor 9 promoter polymorphism is associated with decreased risk of Alzheimer’s disease in Han Chinese. J Neuroinflammation. 2013;10(1):101.
74. Block ML, Hong JS. Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol. 2005;76(2):77–98.
75. Wynne AM, Henry CJ, Godbout JP. Immune and behavioral consequences of microglial reactivity in the aged brain. Integr Comp Biol. 2009;49(3):254–66.
76. Tucsek Z, et al. Obesity in aging exacerbates blood–brain barrier disruption, neuroinflammation, and oxidative stress in the mouse hippocampus: effects on expression of genes involved in beta-amyloid generation and Alzheimer’s disease. J Gerontol A Biol Sci Med Sci. 2014;69:1212–26.
77. Park SM et al. Effects of collagen-induced rheumatoid arthritis on amyloidosis and microvascular pathology in APP/PS1 mice. BMC Neurosci. 2011;12:106.
78. Boyd TD et al. GM-CSF upregulated in rheumatoid arthritis reverses cognitive impairment and amyloidosis in Alzheimer mice. J Alzheimers Dis. 2010;21(2):507–18. doi:10.3233/JAD-2010-091471. These authors showed that subcutaneous GM-CSF administration significantly reduced brain amyloidosis and completely reversed the cognitive impairment, while increasing hippocampal synaptic area and microglial density in mice model.
79. Misiak B, Leszek J, Kiejna A. Metabolic syndrome, mild cognitive impairment and Alzheimer’s disease—the emerging role of systemic low-grade inflammation and adiposity. Brain Res Bull. 2012;89(3–4):144–9.
80. Doruk H et al. The relationship between body mass index and incidental mild cognitive impairment, Alzheimer’s disease and vascular dementia in elderly. J Nutr Health Aging. 2010;14(10):834–8.
81. Ho AJ et al. Obesity is linked with lower brain volume in 700 AD and MCI patients. Neurobiol Aging. 2010;31(8):1326–39.
82. Naorungroj S et al. Cognitive decline and oral health in middle-aged adults in the ARIC study. J Dent Res. 2013;92(9):795–801.
83. Noble JM et al. Periodontitis is associated with cognitive impairment among older adults: analysis of NHANES-III. J Neurol Neurosurg Psychiatry. 2009;80(11):1206–11.
84. 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.
85. Ferraccioli G et al. Rheumatoid arthritis and Alzheimer’s disease: genetic and epigenetic links in inflammatory regulation. Discov Med. 2012;14(79):379–88.
86. Aisen PS et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA. 2003;289(21):2819–26.
87. Soininen H et al. Long-term efficacy and safety of celecoxib in Alzheimer’s disease. Dement Geriatr Cogn Disord. 2007;23(1):8–21.
88. Leoutsakos JM et al. Effects of non-steroidal anti-inflammatory drug treatments on cognitive decline vary by phase of pre-clinical Alzheimer disease: findings from the randomized controlled Alzheimer’s disease anti-inflammatory prevention trial. Int J Geriatr Psychiatr. 2012;27(4):364–74. doi:10.1002/gps.2723. This recent revision of the AD Anti-inflammatory Prevention Trial supports a beneficial role of NSAID only in the early, asymptomatic, phases of Alzheimer disease suggesting that neuroinflammation could be a crucial events in the neurodegeneration process.
89. Breitner JC et al. Extended results of the Alzheimer’s disease anti-inflammatory prevention trial. Alzheimers Dement. 2011;7(4):402–11.
90. Hirsch EC, Vyas S, Hunot S. Neuroinflammation in Parkinson’s disease. Parkinsonism Relat Disord. 2012;18 Suppl 1:S210–2.
91. Matsuda R et al. Quantitive cytokine mRNA expression profiles in the colonic mucosa of patients with steroid naive ulcerative colitis during active and quiescent disease. Inflamm Bowel Dis. 2009;15(3):328–34.
92. Devos D et al. Colonic inflammation in Parkinson’s disease. Neurobiol Dis. 2013;50:42–8.
93. Chen H et al. Nonsteroidal antiinflammatory drug use and the risk for Parkinson’s disease. Ann Neurol. 2005;58(6):963–7.
94. Wahner AD et al. Nonsteroidal anti-inflammatory drugs may protect against Parkinson disease. Neurology. 2007;69(19):1836–42.
95. Leung E et al. Microglia activation mediates fibrillar amyloid-beta toxicity in the aged primate cortex. Neurobiol Aging. 2011;32(3):387–97.
96. Frautschy SA et al. Microglial response to amyloid plaques in APPsw transgenic mice. Am J Pathol. 1998;152(1):307–17.
97. Cagnin A, Gerhard A, Banati RB. In vivo imaging of neuroinflammation. Eur Neuropsychopharmacol. 2002;12(6):581–6.
98. Cosenza-Nashat M et al. Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain. Neuropathol Appl Neurobiol. 2009;35(3):306–28.
99. Shah F et al. Synthesis of the enantiomers of [N-methyl-11C]PK 11195 and comparison of their behaviours as radioligands for PK binding sites in rats. Nucl Med Biol. 1994;21(4):573–81.
100. Chauveau F et al. Nuclear imaging of neuroinflammation: a comprehensive review of [11C]PK11195 challengers. Eur J Nucl Med Mol Imaging. 2008;35(12):2304–19.
101. Politis M, Su P, Piccini P. Imaging of microglia in patients with neurodegenerative disorders. Front Pharmacol. 2012;3:96.
102. Yasuno F et al. Increased binding of peripheral benzodiazepine receptor in mild cognitive impairment-dementia converters measured by positron emission tomography with [(1)(1)C]DAA1106. Psychiatry Res. 2012;203(1):67–74.
103. Edison P et al. Microglia, amyloid, and cognition in Alzheimer’s disease: an [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis. 2008;32(3):412–9.
104. Cagnin A et al. In vivo detection of microglial activation in frontotemporal dementia. Ann Neurol. 2004;56(6):894–7.
105. McGeer PL et al. Microglia in degenerative neurological disease. Glia. 1993;7(1):84–92.
106. Lant SB RA, Thompson JC, Rollinson S, Pickering-Brown S, Snowden JS, Davidson YS, Gerhard A, Mann DM. Patterns of microglial cell activation in frontotemporal lobar degeneration. Neuropathol Appl Neurobiol. 2014;40:686–96.
107. Maeda J et al. Novel peripheral benzodiazepine receptor ligand [11C]DAA1106 for PET: an imaging tool for glial cells in the brain. Synapse. 2004;52(4):283–91.
108. Wang M, Gao M, Zheng QH. Fully automated synthesis of PET TSPO radioligands [11C]DAA1106 and [18 F]FEDAA1106. Appl Radiat Isot. 2012;70(6):965–73.
109. Yasuno F et al. Increased binding of peripheral benzodiazepine receptor in Alzheimer’s disease measured by positron emission tomography with [11C]DAA1106. Biol Psychiatry. 2008;64(10):835–41.
110. Venneti S, Lopresti BJ, Wiley CA. Molecular imaging of microglia/macrophages in the brain. Glia. 2013;61(1):10–23. doi:10.1002/glia.22357. This review provides an interesting and updated overview of positron emission tomography (PET) and magnetic resonance (MR) imaging of microglia/macrophages in the brain.
111. Yoder KK et al. Influence of TSPO genotype on 11C-PBR28 standardized uptake values. J Nucl Med. 2013;54(8):1320–2. doi:10.2967/jnumed.112.118885. This was one of the first study showing the effect of TSPO genotype on the binding potential of new microglial cell PET tracers.
112. Kreisl WC et al. A genetic polymorphism for translocator protein 18 kDa affects both in vitro and in vivo radioligand binding in human brain to this putative biomarker of neuroinflammation. J Cereb Blood Flow Metab. 2013;33(1):53–8.
113. Kreisl WC et al. In vivo radioligand binding to translocator protein correlates with severity of Alzheimer’s disease. Brain. 2013;136(Pt 7):2228–38.
114. Fan Z, et al. Influence of microglial activation on neuronal function in Alzheimer’s and Parkinson’s disease dementia. Alzheimers Dement. 2014. doi:10.1016/j.jalz.2014.06.016.