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Chapter 10 - Role of Inflammation in Lewy Body Dementia

Published online by Cambridge University Press:  02 September 2021

By
Ajenthan Surendranathan  and
John T. O’Brien
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

Lewy body dementia (LBD) is an umbrella term used to group together the two closely related conditions of dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD). Cortical neuronal Lewy bodies and Lewy neurites are found in both conditions at autopsy. As well as dementia, DLB and PDD also share common clinical features including fluctuations in attention, visual hallucinations and parkinsonism (1,2). If parkinsonism is present one year before the onset of dementia, patients are diagnosed with PDD, if it is less than one year, or it is not present, the diagnosis is DLB.

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Information
Textbook of Immunopsychiatry , pp. 190 - 212
Publisher: Cambridge University Press
Print publication year: 2021

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References

McKeith, IG, Boeve, BF, Dickson, DW, et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology. 2017;89(1):88–100.Google Scholar
Emre, M, Aarsland, D, Brown, R, et al. Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord. 2007;22(12):1689–707.Google Scholar
Hogan, D, Fiest, KM, Roberts, JI, et al. The prevalence and incidence of dementia with Lewy bodies: a systematic review. Can J Neurol Sci. 2016;43(S1):S83–95.Google Scholar
Vann Jones, SA, O’Brien, JT. The prevalence and incidence of dementia with Lewy bodies: a systematic review of population and clinical studies. Psychol Med. 2014;44(4):673–83.Google Scholar
Hely, MA, Reid, WGJ, Adena, MA, Halliday, GM, Morris, JGL. The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years. Mov Disord. 2008;23(6):837–44.Google Scholar
Aarsland, D, Zaccai, J, Brayne, C. A systematic review of prevalence studies of dementia in Parkinson’s disease. Mov Disord. 2005;20(10):1255–63.Google Scholar
Fujimi, K, Sasaki, K, Noda, K, et al. Clinicopathological outline of dementia with Lewy bodies applying the revised criteria: the Hisayama study. Brain Pathol. 2008;18(3):317–25.Google Scholar
McGeer, PL, McGeer, EG. The amyloid cascade-inflammatory hypothesis of Alzheimer disease: Implications for therapy. Acta Neuropathol. 2013;126(4):479–97.Google Scholar
Hamelin, L, Lagarde, J, Dorothé, G, et al. Early and protective microglial activation in Alzheimer’s disease: a prospective study using 18 F-DPA-714 PET imaging. Brain. 2016;139(4):1252–64.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.Google Scholar
Lee, Y-J, Han, SB, Nam, S-Y, Oh, K-W, Hong, JT. Inflammation and Alzheimer’s disease. Arch Pharm Res. 2010;33(10):1539–56.Google Scholar
Ginhoux, F, Lim, S, Hoeffel, G, Low, D, Huber, T. Origin and differentiation of microglia. Front Cell Neurosci. 2013;7(April):1–14.Google Scholar
Nayak, D, Roth, TL, McGavern, DB. Microglia development and function. Annu Rev Immunol. 2014;32:367–402.Google Scholar
Nimmerjahn, A, Kirchhoff, F, Helmchen, F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science. 2005;308(5726):1314–8.Google Scholar
Dardiotis, E, Siokas, V, Pantazi, E, et al. A novel mutation in TREM2 gene causing Nasu-Hakola disease and review of the literature. Neurobiol Aging. 2017;53:194.e13–194.e22.Google Scholar
Ransohoff, RM. How neuroinflammation contributes to neurodegeneration. Science. 2016;353(6301):777–83.Google Scholar
Yeh, FL, Hansen, D V., Sheng, M. TREM2, microglia, and neurodegenerative diseases. Trends Mol Med. 2017;23(6):512–33.Google Scholar
Atagi, Y, Liu, C-C, Painter, MM, et al. Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2). J Biol Chem. 2015;290(43):26043–50.Google Scholar
Gao, H, Liu, B, Zhang, W, Hong, J. Critical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson’s disease. FASEB J. 2003;17(13):1954–6.Google Scholar
Prinz, M, Priller, J. Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat Rev Neurosci. 2014;15(5):300–12.Google Scholar
Bliederhaeuser, C, Grozdanov, V, Speidel, A, et al. Age-dependent defects of alpha-synuclein oligomer uptake in microglia and monocytes. Acta Neuropathol. 2016;131(3):379–91.Google Scholar
Perry, VH, Holmes, C. Microglial priming in neurodegenerative disease. Nat Rev Neurol. 2014;10(4):217–24.Google Scholar
Gao, H-M, Hong, J-S. Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol. 2008;29(8):357–65.Google Scholar
Colombo, E, Farina, C. Astrocytes: key regulators of neuroinflammation. Trends Immunol. 2016;37(9):608–20.Google Scholar
Spillantini, MG, Schmidt, ML, Lee, VM, et al. Alpha-synuclein in Lewy bodies. Nature. 1997;388(6645):839–40.Google Scholar
Lashuel, H a, Overk, CR, Oueslati, A, Masliah, E. The many faces of α-synuclein: from structure and toxicity to therapeutic target. Nat Rev Neurosci. 2013;14(1):38–48.Google Scholar
Bartels, T, Choi, JG, Selkoe, DJ. α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature. 2011;477(7362):107–10.Google Scholar
Zhang, WW, Wang, T, Pei, Z, et al. Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. FASEB J. 2005;19(6):533–42.Google Scholar
Zhang, W, Dallas, S, Zhang, D, et al. Microglial PHOX and Mac-1 are essential to the enhanced dopaminergic neurodegeneration elicited by A30P and A53T mutant alpha-synuclein. Glia. 2007;55(11):1178–88.Google Scholar
Theodore, S, Cao, S, McLean, PJ, Standaert, DG. Targeted overexpression of human alpha-synuclein triggers microglial activation and an adaptive immune response in a mouse model of Parkinson disease. J Neuropathol Exp Neurol. 2008;67(12):1149–58.Google Scholar
Hoffmann, A, Ettle, B, Bruno, A, et al. Alpha-synuclein activates BV2 microglia dependent on its aggregation state. Biochem Biophys Res Commun. 2016;479(4):881–6.Google Scholar
Daniele, SG, Béraud, D, Davenport, C, et al. Activation of MyD88-dependent TLR1/2 signaling by misfolded α-synuclein, a protein linked to neurodegenerative disorders. Sci Signal. 2015;8(376):ra45.Google Scholar
Kim, WS, Kågedal, K, Halliday, GM. Alpha-synuclein biology in Lewy body diseases. Alzheimers Res Ther. 2014;6(5):73.Google Scholar
Fellner, L, Irschick, R, Schanda, K, et al. Toll-like receptor 4 is required for α-synuclein dependent activation of microglia and astroglia. Glia. 2013;61(3):349–60.Google Scholar
Kim, C, Ho, D-H, Suk, J-E, et al. Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia. Nat Commun. 2013;4:1562.Google Scholar
Venezia, S, Refolo, V, Polissidis, A, et al. Toll-like receptor 4 stimulation with monophosphoryl lipid A ameliorates motor deficits and nigral neurodegeneration triggered by extraneuronal α-synucleinopathy. Mol Neurodegener. 2017;12(1):1–13.Google Scholar
La Vitola, P, Balducci, C, Cerovic, M, et al. Alpha-synuclein oligomers impair memory through glial cell activation and via Toll-like receptor 2. Brain Behav Immun. 2018;69:591–602.Google Scholar
Nash, KR, Moran, P, Finneran, DJ, et al. Fractalkine over expression suppresses α -synuclein-mediated neurodegeneration. Mol Ther. 2015;23(1):17–23.Google Scholar
Thome, AD, Standaert, DG, Harms, AS. Fractalkine signaling regulates the inflammatory response in an α-synuclein model of Parkinson disease. PLoS One. 2015;10(10):1–13.Google Scholar
Lastres-Becker, I, Ulusoy, A, Innamorato, NG, et al. α-Synuclein expression and Nrf2 deficiency cooperate to aggravate protein aggregation, neuronal death and inflammation in early-stage Parkinson’s disease. Hum Mol Genet. 2012;21(14):3173–92.Google Scholar
Lastres-Becker, I, García-Yagüe, AJ, Scannevin, RH, et al. Repurposing the NRF2 activator dimethyl fumarate as therapy against synucleinopathy in Parkinson’s disease. Antioxid Redox Signal. 2016;25(2):61–77.Google Scholar
Sharma, N, Nehru, B. Characterization of the lipopolysaccharide induced model of Parkinson’s disease: role of oxidative stress and neuroinflammation. Neurochem Int. 2015;87:92–105.Google Scholar
Tanaka, S, Ishii, A, Ohtaki, H, 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.Google Scholar
Wang, M-X, Cheng, X-Y, Jin, M, et al. TNF compromises lysosome acidification and reduces α-synuclein degradation via autophagy in dopaminergic cells. Exp Neurol. 2015;271:112–21.Google Scholar
Daher, JPL, Volpicelli-Daley, LA, Blackburn, JP, Moehle, MS, West, AB. Abrogation of α-synuclein-mediated dopaminergic neurodegeneration in LRRK2-deficient rats. Proc Natl Acad Sci USA. 2014;111(25):9289–94.Google Scholar
Daher, JPL, Abdelmotilib, HA, Hu, X, et al. Leucine-rich repeat kinase 2 (LRRK2) pharmacological inhibition abates α-synuclein gene-induced neurodegeneration. J Biol Chem. 2015;290(32):19433–44.Google Scholar
Maekawa, T, Sasaoka, T, Azuma, S, et al. Leucine-rich repeat kinase 2 (LRRK2) regulates α-synuclein clearance in microglia. BMC Neurosci. 2016;17(1):1–12.Google Scholar
Cao, S, Standaert, DG, Harms, AS. The gamma chain subunit of Fc receptors is required for alpha-synuclein-induced pro-inflammatory signaling in microglia. J Neuroinflammation. 2012;9(1):259.Google Scholar
Choi, YR, Kang, SJ, Kim, JM, et al. FcγRIIB mediates the inhibitory effect of aggregated α-synuclein on microglial phagocytosis. Neurobiol Dis. 2015;83:90–9.Google Scholar
Harms, AS, Cao, S, Rowse, AL, et al. MHCII is required for α-synuclein-induced activation of microglia, CD4 T cell proliferation, and dopaminergic neurodegeneration. J Neurosci. 2013;33(23):9592–600.Google Scholar
Harms, AS, Thome, AD, Yan, Z, et al. Peripheral monocyte entry is required for alpha-synuclein induced inflammation and neurodegeneration in a model of Parkinson disease. Exp Neurol. 2018;300(August2017):179–87.Google Scholar
Jin, J, Shie, F-S, Liu, J, et al. Prostaglandin E2 receptor subtype 2 (EP2) regulates microglial activation and associated neurotoxicity induced by aggregated alpha-synuclein. J Neuroinflammation. 2007;4:2.Google Scholar
Qin, H, Buckley, JA, Li, X, et al. Inhibition of the JAK/STAT pathway protects against α-synuclein-induced neuroinflammation and dopaminergic neurodegeneration. J Neurosci. 2016;36(18):5144–59.Google Scholar
Wang, S, Chu, C-H, Stewart, T, et al. α-Synuclein, a chemoattractant, directs microglial migration via H2O2-dependent Lyn phosphorylation. Proc Natl Acad Sci USA. 2015;112(15):E1926–35.Google Scholar
Kim, C, Cho, E-D, Kim, H-K, et al. Β1-integrin-dependent migration of microglia in response to neuron-released a-synuclein. Exp Mol Med. 2014;46(4):e91.Google Scholar
Boza-Serrano, A, Reyes, JF, Rey, NL, et al. The role of Galectin-3 in α-synuclein-induced microglial activation. Acta Neuropathol Commun. 2014;2(1):156.Google Scholar
Wang, W, Nguyen, LTT, Burlak, C, et al. Caspase-1 causes truncation and aggregation of the Parkinson’s disease-associated protein α-synuclein. Proc Natl Acad Sci. 2016;113(34):9587–92.Google Scholar
Fan, Z, Aman, Y, Ahmed, I, et al. Influence of microglial activation on neuronal function in Alzheimer’s and Parkinson’s disease dementia. Alzheimers Dement. 2015;11(6):608–21.e7.Google Scholar
Gerhard, A, Banati, RB, Goerres, GB, et al. [11C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy. Neurology. 2003;61(5):686–9.Google Scholar
Edison, P, Archer, HA, Gerhard, A, 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.Google Scholar
Ouchi, Y, Yoshikawa, E, Sekine, Y, et al. Microglial activation and dopamine terminal loss in early Parkinson’s disease. Ann Neurol. 2005;57(2):168–75.Google Scholar
Gerhard, A, Pavese, N, Hotton, G, et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol Dis. 2006;21(2):404–12.Google Scholar
Braak, H, Tredici K, Del, Rüb, U, et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 2003;24(2):197–211.Google Scholar
Terada, T, Yokokura, M, Yoshikawa, E, et al. Extrastriatal spreading of microglial activation in Parkinson’s disease: a positron emission tomography study. Ann Nucl Med. 2016;30(8):579–87.Google Scholar
Kobayashi, M, Jiang, T, Telu, S, et al. 11C-DPA-713 has much greater specific binding to translocator protein 18 kDa (TSPO) in human brain than11C-(R)-PK11195. J Cereb Blood Flow Metab. 2018;38(3):393–403.Google Scholar
Owen, DR, Yeo, AJ, Gunn, RN, et al. An 18-kDa Translocator Protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab. 2012;32(1):1–5.Google Scholar
Edison, P, Ahmed, I, Fan, Z, et al. Microglia, amyloid, and glucose metabolism in Parkinson’s disease with and without dementia. Neuropsychopharmacology. 2013;38(6):938–49.Google Scholar
Iannaccone, S, Cerami, C, Alessio, M, 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.Google Scholar
Femminella, GD, Ninan, S, Atkinson, R, et al. Does microglial activation influence hippocampal volume and neuronal function in Alzheimer’s disease and Parkinson’s disease dementia? J Alzheimer’s Dis. 2016;51(4):1275–89.Google Scholar
Högl, B, Stefani, A, Videnovic, A. Idiopathic REM sleep behaviour disorder and neurodegeneration – an update. Nat Rev Neurol. 2018;14(1):40–56.Google Scholar
Stokholm, MG, Iranzo, A, Østergaard, K, et al. Assessment of neuroinflammation in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study. Lancet Neurol. 2017;16(10):789–96.Google Scholar
Stokholm, MG, Iranzo, A, Østergaard, K, et al. Extrastriatal monoaminergic dysfunction and enhanced microglial activation in idiopathic rapid eye movement sleep behaviour disorder. Neurobiol Dis. 2018;115(January):9–16.Google Scholar
McGeer, PL, Itagaki, S, Boyes, BE, McGeer, EG. 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.Google Scholar
Imamura, K, Hishikawa, N, Sawada, M, 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.Google Scholar
Walker, DG, Lue, LF, Serrano, G, et al. Altered expression patterns of inflammation-associated and trophic molecules in substantia nigra and striatum brain samples from Parkinson’s disease, incidental Lewy body disease and normal control cases. Front Neurosci. 2016;9(Jan):1–18.Google Scholar
Brochard, V, Combadière, B, Prigent, A, 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.Google Scholar
Mogi, M, Harada, M, Kondo, T, et al. Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. Neurosci Lett. 1994;180(2):147–50.Google Scholar
Loeffler, DA, Camp, DM, Conant, SB. Complement activation in the Parkinson’s disease substantia nigra: an immunocytochemical study. J Neuroinflammation. 2006;3:29.Google Scholar
Dzamko, N, Gysbers, A, Perera, G, et al. Toll-like receptor 2 is increased in neurons in Parkinson’s disease brain and may contribute to alpha-synuclein pathology. Acta Neuropathol. 2017;133(2):303–19.Google Scholar
Wakabayashi, K, Hayashi, S, Yoshimoto, M, Kudo, H, Takahashi, H. NACP/alpha-synuclein-positive filamentous inclusions in astrocytes and oligodendrocytes of Parkinson’s disease brains. Acta Neuropathol. 2000;99(1):14–20.Google Scholar
Braak, H, Sastre, M, Del Tredici, K. Development of α-synuclein immunoreactive astrocytes in the forebrain parallels stages of intraneuronal pathology in sporadic Parkinson’s disease. Acta Neuropathol. 2007;114(3):231–41.Google Scholar
Togo, T, Iseki, E, Marui, W, et al. Glial involvement in the degeneration process of Lewy body-bearing neurons and the degradation process of Lewy bodies in brains of dementia with Lewy bodies. J Neurol Sci. 2001;184(1):71–5.Google Scholar
Mackenzie, IR. Activated microglia in dementia with Lewy bodies. Neurology. 2000;55:132–4.Google Scholar
Shepherd, CE, Thiel, E, Mccann, H, Harding, AJ, Halliday, GM. Cortical inflammation in Alzheimer disease but not dementia with Lewy bodies. Arch Neurol. 2015;57(6):817–22.Google Scholar
Streit, WJ, Xue, QS. Microglia in dementia with Lewy bodies. Brain Behav Immun. 2016;55:191–201.Google Scholar
Bachstetter, AD, Van Eldik, LJ, Schmitt, FA, et al. Disease-related microglia heterogeneity in the hippocampus of Alzheimer’s disease, dementia with Lewy bodies, and hippocampal sclerosis of aging. Acta Neuropathol Commun. 2015;3(1):1–16.Google Scholar
Walker, DG, Lue, LF, Tang, TM, et al. Changes in CD200 and intercellular adhesion molecule-1 (ICAM-1) levels in brains of Lewy body disorder cases are associated with amounts of Alzheimer’s pathology not α-synuclein pathology. Neurobiol Aging. 2017;54:175–86.Google Scholar
Garcia-Esparcia, P, López-González, I, Grau-Rivera, O, et al. Dementia with Lewy bodies: molecular pathology in the frontal cortex in typical and rapidly progressive forms. Front Neurol. 2017;8:89.Google Scholar
Wahner, AD, Sinsheimer, JS, Bronstein, JM, Ritz, B. Inflammatory cytokine gene polymorphisms and increased risk of Parkinson disease. Arch Neurol. 2007;64(6):836–40.Google Scholar
McGeer, PL, Yasojima, K, McGeer, EG. Association of interleukin-1β polymorphisms with idiopathic Parkinson’s disease. Neurosci Lett. 2002;326(1):67–9.Google Scholar
Rayaprolu, S, Mullen, B, Baker, M, et al. TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson’s disease. Mol Neurodegener. 2013;8(1):19.Google Scholar
Alessi, DR, Sammler, E. LRRK2 kinase in Parkinson’s disease. Science. 2018;360(6384):36–7.Google Scholar
Hamza, TH, Zabetian, CP, Tenesa, A, et al. Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease. Nat Genet. 2010;42(9):781–5.Google Scholar
Nalls, MA, Plagnol, V, Hernandez, DG, et al. Imputation of sequence variants for identification of genetic risks for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet. 2011;377(9766):641–9.Google Scholar
Nalls, MA, Pankratz, N, Lill, CM, et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nat Genet. 2014;46(9):989–93.Google Scholar
Wissemann, WT, Hill-Burns, EM, Zabetian, CP, et al. Association of Parkinson disease with structural and regulatory variants in the HLA region. Am J Hum Genet. 2013;93(5):984–93.Google Scholar
Kannarkat, GT, Cook, DA, Lee, J-K, et al. Common genetic variant association with altered HLA expression, synergy with pyrethroid exposure, and risk for Parkinson’s disease: an observational and case–control study. NPJ Park Dis. 2015;1(January):15002.Google Scholar
Guerreiro, R, Ross, OA, Kun-Rodrigues, C, et al. Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study. Lancet Neurol. 2018;17(1):64–74.Google Scholar
Guerreiro, R, Ross, OA, Kun-Rodrigues, C, et al. Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study. Lancet Neurol. 2018;17(1):64–74.Google Scholar
Chen, H, O’Reilly, EJ, Schwarzschild, MA, Ascherio, A. Peripheral inflammatory biomarkers and risk of Parkinson’s disease. Am J Epidemiol. 2008;167(1):90–5.Google Scholar
Dobbs, RJ, Charlett, A, Purkiss, AG, et al. Association of circulating TNF-alpha and IL-6 with ageing and parkinsonism. Acta Neurol Scand. 1999;100(1):34–41.Google Scholar
Hu, Y, Yu, S, Zuo, L, et al. Parkinson disease with REM sleep behavior disorder: Features, α-synuclein, and inflammation. Neurology. 2015;84(9):888–94.Google Scholar
Rentzos, M, Nikolaou, C, Andreadou, E, et al. Circulating interleukin-15 and RANTES chemokine in Parkinson’s disease. Acta Neurol Scand. 2007;116(6):374–9.Google Scholar
Umemura, A, Oeda, T, Yamamoto, K, et al. Baseline plasma C-reactive protein concentrations and motor prognosis in Parkinson disease. PLoS One. 2015;10(8):1–12.Google Scholar
Bas, J, Calopa, M, Mestre, M, et al. Lymphocyte populations in Parkinson’s disease and in rat models of parkinsonism. J Neuroimmunol. 2001;113:146–52.Google Scholar
Song, I-U, Kim, Y-D, Cho, H-J, Chung, S-W. Is Neuroinflammation Involved in the Development of Dementia in Patients with Parkinson’s Disease? Intern Med. 2013;52(16):1787–92.Google Scholar
King, E, O’Brien, JT, Donaghy, P, et al. Peripheral inflammation in prodromal Alzheimer’s and Lewy body dementias. J Neurol Neurosurg Psychiatry. 2018;89:339–45.Google Scholar
Mogi, M, Harada, M, Riederer, P, et al. Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett. 1994;165(1–2):208–10.Google Scholar
Delgado-Alvarado, M, Gago, B, Gorostidi, A, et al. Tau/α-synuclein ratio and inflammatory proteins in Parkinson’s disease: An exploratory study. Mov Disord. 2017;32(7):1066–73.Google Scholar
Blum-Degen, D, Müller, T, Kuhn, W, et al. Interleukin-1β and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer’s and de novo Parkinson’s disease patients. Neurosci Lett. 1995;202(1–2):17–20.Google Scholar
Müller, T, Blum-Degen, D, Przuntek, H, Kuhn, W. Interleukin-6 levels in cerebrospinal fluid inversely correlate to severity of Parkinson’s disease. Acta Neurol Scand. 1998;98(2):142–4.Google Scholar
Yu, S-Y, Zuo, L-J, Wang, F, et al. Potential biomarkers relating pathological proteins, neuroinflammatory factors and free radicals in PD patients with cognitive impairment: a cross-sectional study. BMC Neurol. 2014;14(1):113.Google Scholar
Shi, M, Bradner, J, Hancock, AM, et al. Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression. Ann Neurol. 2011;69(3):570–80.Google Scholar
Miyajima, M, Nakajima, M, Motoi, Y, et al. Leucine-rich α2-glycoprotein is a novel biomarker of neurodegenerative disease in human cerebrospinal fluid and causes neurodegeneration in mouse cerebral cortex. PLoS One. 2013;8(9):e74453.Google Scholar
Ernst, A, Morgenthaler, NG, Buerger, K, et al. Procalcitonin is elevated in the cerebrospinal fluid of patients with dementia and acute neuroinflammation. J Neuroimmunol. 2007;189(1–2):169–74.Google Scholar
Hall, S, Surova, Y, Öhrfelt, A, et al. Longitudinal Measurements of Cerebrospinal Fluid Biomarkers in Parkinson’s Disease. Mov Disord. 2016;31(6):898–905.Google Scholar
Wennström, M, Surova, Y, Hall, S, et al. The inflammatory marker YKL-40 is elevated in cerebrospinal fluid from patients with Alzheimer’s but not Parkinson’s disease or dementia with Lewy bodies. PLoS One. 2015;10(8):1–13.Google Scholar
Janelidze, S, Hertze, J, Zetterberg, H, et al. Cerebrospinal fluid neurogranin and YKL-40 as biomarkers of Alzheimer’s disease. Ann Clin Transl Neurol. 2016;3(1):12–20.Google Scholar
Gagne, JJ, Power, MC. Anti-inflammatory drugs and risk of Parkinson disease: a meta-analysis. Neurology. 2010;74(12):995–1002.Google Scholar
Samii, A, Etminan, M, Wiens, MO, Jafari, S. NSAID use and the risk of Parkinson’s disease: systematic review and meta-analysis of observational studies. Drugs Aging. 2009;26(9):769–79.Google Scholar
Orr, CF, Rowe, DB, Mizuno, Y, Mori, H, Halliday, GM. A possible role for humoral immunity in the pathogenesis of Parkinson’s disease. Brain. 2005;128(Pt 11):2665–74.Google Scholar
Harms, AS, Delic, V, Thome, AD, et al. α-Synuclein fibrils recruit peripheral immune cells in the rat brain prior to neurodegeneration. Acta Neuropathol Commun. 2017;5(1):85.Google Scholar
Surendranathan, A, Rowe, JB, O’Brien, JT. Neuroinflammation in Lewy body dementia. Park Relat Disord. 2015;21(12):1398–406.Google Scholar

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