Abstract:Alzheimer?s disease (AD) is a progressive neurodegenerative disease, and the pathogenesis of AD has not been fully elucidated. Patients with AD had higher seropositivity rates for anti-Toxoplasma gondii (T. gondii) IgG antibodies compared to healthy controls. T. gondii infection caused AD-like symptoms (cognitive impairment, memory loss); infected wild-type mice showed major signs of AD including Aβ deposition, pTau expression, and neuronal loss. Results of researches indicate a possible link between T. gondii infection and AD. In this review, we summarized recent advances on the association between T. gondii infection and AD.
郑斌, 李金娜. 弓形虫感染与阿尔茨海默病相关性的研究进展[J]. 中国人兽共患病学报, 2018, 34(10): 931-935.
ZHENG Bin, LI Jin-na. Advances on the association between Toxoplasma gondii infection and Alzheimer?s disease. Chinese Journal of Zoonoses, 2018, 34(10): 931-935.
[1] Alzheimer?s Association. 2016 Alzheimer?s disease facts and figures[J]. Alzheimers Dement, 2016, 12(4):459-509. [2] Shubhakaran KP, Khichar RJ.Dementia in China: current status[J]. Neurology, 2014, 82(14):1291. DOI: 10.1212/WNL.0000000000000233 [3] Weinreb O, Mandel S, Bar-Am O, et al.Iron-chelating backbone coupled with monoamine oxidase inhibitory moiety as novel pluripotential therapeutic agents for Alzheimer?s disease: a tribute to Moussa Youdim[J]. J Neural Transm (Vienna), 2011, 118(3):479-492. DOI: 10.1007/s00702-011-0597-6 [4] Lim C, Hammond CJ, Hingley ST, et al.Chlamydia pneumoniae infection of monocytes in vitro stimulates innate and adaptive immune responses relevant to those in Alzheimer?s disease[J]. J Neuroinflammation, 2014, 11:217. DOI: 10.1186/s12974-014-0217-0 [5] 杨新玲, 刘雪晴, 杨杰民. 肺炎衣原体感染与阿尔茨海默病的关系[J]. 中国人兽共患病学报,2013,29(2):195-198. DOI:103969/cjz.j.issn1002-2694.2013.01.020 [6] Kountouras J, Boziki M, Zavos C, et al.A potential impact of chronic Helicobacter pylori infection on Alzheimer?s disease pathobiology and course[J]. Neurobiol Aging, 2012, 33:e3-e4. DOI: 10.1016/j.neurobiolaging.2012.01.003 [7] Prandota J.Possible link between Toxoplasma Gondii and the anosmia associated with neurodegenerative diseases[J]. Am J Alzheimers Dis, 2014, 29:205-214. DOI: 10.1177/1533317513517049 [8] Borjabad A, Volsky DJ.Common transcriptional signatures in brain tissue from patients with HIV-associated neurocognitive disorders, Alzheimer?s disease, and Multiple Sclerosis[J]. J Neuroimmune Pharmacol, 2012, 7:914-926. DOI: 10.1007/s11481-012-9409-5 [9] Lurain NS, Hanson BA, Martinson J, et al.Virological and immunological characteristics of human cytomegalovirus infection associated with Alzheimer?s disease[J]. J Infect Dis, 2013, 208:564-572. DOI: 10.1093/infdis/jit210 [10] Berenreiterová M, Flegr J, Kuběna AA, et al.The distribution of Toxoplasma gondii cysts in the brain of a mouse with latent toxoplasmosis: implications for the behavioral manipulation hypothesis[J]. PLoS One, 2011, 6(12):e28925. DOI: 10.1371/journal.pone.0028925 [11] Vyas A, Sapolsky R.Manipulation of host behaviour by Toxoplasma gondii: what is the minimum a proposed proximate mechanism should explain[J]. Folia Parasitol (Praha), 2010, 57(2):88-94. [12] Torrey EF, Bartko JJ, Yolken RH.Toxoplasma gondii and other risk factors for schizophrenia: an update[J]. Schizophr Bull, 2012, 38(3):642-647. DOI: 10.1093/schbul/sbs043 [13] Kusbeci OY, Miman O, Yaman M, et al.Could Toxoplasma gondii have any role in Alzheimer disease[J]. Alzheimer Dis Assoc Disord, 2011, 25(1):1-3. DOI: 10.1097/WAD.0b013e3181f73bc2 [14] Fekadu A, Shibre T, Cleare AJ.Toxoplasmosis as a cause for behaviour disorders-overview of evidence and mechanisms[J]. Folia Parasitol (Praha), 2010, 57(2):105-113. [15] Berrett AN, Gale SD, Erickson LD, et al.Toxoplasma gondii moderates the association between multiple Folate-Cycle factors and cognitive function in U.S. adults[J]. Nutrients, 2017, 9(6):564. DOI: 10.3390/nu9060564 [16] Gale SD, Brown BL, Erickson LD, et al.Association between latent toxoplasmosis and cognition in adults: a cross-sectional study[J]. Parasitology, 2015, 142(4):557-565. DOI: 10.1017/S0031182014001577 [17] Mendy A, Vieira ER, Albatineh AN, et al.Immediate rather than delayed memory impairment in older adults with latent toxoplasmosis[J]. Brain Behav Immun, 2015, 45:36-40. DOI: 10.1016/j.bbi.2014.12.006 [18] Gajewski PD, Falkenstein M, Hengstler JG, et al.Toxoplasma gondii impairs memory in infected seniors[J]. Brain Behav Immun, 2014, 36:193-199. DOI: 10.1016/j.bbi.2013.11.019 [19] Nimgaonkar VL, Yolken RH, Wang T, et al.Temporal cognitive decline associated with exposure to infectious agents in a population-based, aging Cohort[J]. Alzheimer Dis Assoc Disord, 2016, 30(3):216-222. DOI: 10.1097/WAD.00000000-00000133 [20] Yahya RS, Awad SI, El-Baz HA, et al.Impact of ApoE genotypes variations on Toxoplasma patients with dementia[J]. J Clin Neurosci, 2017, 39:184-188. DOI: 10.1016/j.jocn.2017.01.009 [21] House PK, Vyas A, Sapolsky R.Predator cat odors activate sexual arousal pathways in brains of Toxoplasma gondii infected rats[J]. PLoS One, 2011, 6(8):e23277. DOI: 10.1371/journal.pone.0023277 [22] Mahmoudvand H, Sheibani V, Shojaee S, et al.Toxoplasma gondii infection potentiates cognitive impairments of Alzheimer?s Disease in the BALB/c mice[J]. J Parasitol, 2016, 102(6):629-635. DOI: 10.1645/16-28 [23] Mahmoudvand H, Ziaali N, Aghaei I, et al.The possible association between Toxoplasma gondii infection and risk of anxiety and cognitive disorders in BALB/c mice[J]. Pathog Glob Health, 2015, 109(8):369-376. DOI: 10.1080/20477724.2015.1117742 [24] Torres L, Robinson SA, Kim DG, et al.Toxoplasma gondii alters NMDAR signaling and induces signs of Alzheimer?s disease in wild-type, C57BL/6 mice[J]. J Neuroinflammation, 2018, 15(1):57. DOI: 10.1186/s12974-018-1086-8 [25] 周永华, 王小波, 蒋守富, 等. 隐性弓形虫感染小鼠的学习记忆能力障碍研究[J]. 中国寄生虫学与寄生虫病杂志,2011, 29(5):333-338. [26] Daniels BP, Sestito SR, Rouse ST.An expanded task battery in the Morris water maze reveals effects of Toxoplasma gondii infection on learning and memory in rats[J]. Parasitol Int, 2015, 64(1):5-12. DOI: 10.1016/j.parint.2014.09.002 [27] Cabral CM,McGovern KE, MacDonald WR, et al.Dissecting amyloid beta deposition using distinct strains of the neurotropic parasite Toxoplasma gondii as a novel tool[J]. ASN Neuro, 2017, 9(4):1759091417724915. DOI: 10.1177/1759091417724915 [28] Hwang YS, Shin JH, Yang JP, et al.Characteristics of infection immunity regulated by Toxoplasma gondii to maintain chronic infection in the brain[J]. Front Immunol, 2018, 9:158. DOI: 10.3389/fimmu.2018.00158 [29] Parlog A, Harsan LA, Zagrebelsky M, et al.Chronic murine toxoplasmosis is defined by subtle changes in neuronal connectivity[J]. Dis Model Mech, 2014, 7(4):459-469. DOI: 10.1242/dmm.014183 [30] Vutova P, Wirth M, Hippe D, et al.Toxoplasma gondii inhibits Fas/CD95-triggered cell death by inducing aberrant processing and degradation of caspase 8[J]. Cell Microbiol, 2007, 9(6):1556-1570. DOI: 10.1111/j.1462-5822.2007.00893.x [31] Haroon F, Hndel U, Angenstein F, et al.Toxoplasma gondii actively inhibits neuronal function in chronically infected mice[J]. PLoS One, 2012, 7(4):e35516. DOI: 10.1371/journal.pone.0035516 [32] Brooks JM, Carrillo GL, Su J, et al.Toxoplasma gondii infections alter GABAergic synapses and signaling in the central nervous system[J]. MBio, 2015, 6(6):e01428-15. DOI: 10.1128/mBio.01428-15 [33] Kaushik M, Lamberton PH, Webster JP.The role of parasites and pathogens in influencing generalised anxiety and predation-related fear in the mammalian central nervous system[J]. Horm Behav, 2012, 62(3):191-201. DOI: 10.1016/j.yhbeh.2012.04.002 [34] Parlog A, Schlüter D, Dunay IR.Toxoplasma gondii-induced neuronal alterations[J]. Parasite Immunol, 2015,37(3):159-170. DOI: 10.1111/pim.12157 [35] Mahmoud ME, Fereig R, Nishikawa Y.Involvement of host defense mechanisms against Toxoplasma gondii infection in anhedonic and despair-Like behaviors in mice[J]. Infect Immun, 2017, 85(4): e00007-17. DOI: 10.1128/IAI.00007-17 [36] Martin HL, Alsaady I, Howell G, et al.Effect of parasitic infection on dopamine biosynthesis in dopaminergic cells[J].Neuroscience, 2015, 306:50-62. DOI: 10.1016/j.neuroscience.2015.08.005 [37] Gatkowska J, Wieczorek M, Dziadek B, et al.Sex-dependent neurotransmitter level changes in brains of Toxoplasma gondii infected mice[J]. Exp Parasitol, 2013, 133(1):1-7. DOI: 10.1016/j.exppara.2012.10.005 [38] Prandovszky E, Gaskell E, Martin H, et al.The neurotropic parasite Toxoplasma gondii increases dopamine metabolism[J]. PLoS One, 2011, 6(9):e23866. DOI: 10.1371/journal.pone.0023866 [39] Zhang YH, Chen H, Chen Y, et al.Activated microglia contribute to neuronal apoptosis in Toxoplasmic encephalitis[J]. Parasit Vectors, 2014, 7:372. DOI: 10.1186/1756-3305-7-372 [40] Fischer HG, Nitzgen B, Reichmann G, et al.Cytokine responses induced by Toxoplasma gondii in astrocytes and microglial cells[J]. Eur J Immunol, 1997, 27(6):1539-1548. DOI: 10.1002/eji.1830270633 [41] Munoz M, Liesenfeld O, Heimesaat MM.Immunology of Toxoplasma gondii[J]. Immunol Rev, 2011, 240(1):269-285. DOI: 10.1111/j.1600-065X.2010.00992.x [42] McCusker RH, Kelley KW. Immune-neural connections: how the immune system?s response to infectious agents influences behavior[J]. J Exp Biol, 2013, 216(Pt 1):84-98. DOI: 10.1242/jeb.073411 [43] Montacute R, Foley K, Forman R, et al.Enhanced susceptibility of triple transgenic Alzheimer?s disease (3×Tg-AD) mice to acute infection[J]. J Neuroinflammation, 2017, 14(1):50. DOI: 10.1186/s12974-017-0826-5 [44] Carruthers VB, Suzuki Y.Effects of Toxoplasma gondii infection on the brain[J]. Schizophr Bull, 2007, 33(3):745-751. DOI: 10.1093/schbul/sbm008 [45] Leuner K, Schütt T, Kurz C, et al.Mitochondrion-derived reactive oxygen species lead to enhanced amyloid beta formation[J]. Antioxid Redox Signal, 2012, 16(12):1421-1433. DOI: 10.1089/ars.2011.4173 [46] Dincel GC, Atmaca HT.Role of oxidative stress in the pathophysiology of Toxoplasma gondii infection[J]. Int J Immunopathol Pharmacol, 2016, 29(2):226-240. DOI: 10.1177/0394632016638668 [47] Perry CE, Gale SD, Erickson L, et al.Seroprevalence and serointensity of latent Toxoplasma gondii in a sample of elderly adults with and without Alzheimer Disease[J]. Alzheimer Dis Assoc Disord, 2016, 30(2):123-126. DOI: 10.1097/WAD.0000000000000108 [48] Jung BK, Pyo KH, Shin KY, et al.Toxoplasma gondii infection in the brain inhibits neuronal degeneration and learning and memory impairments in a murine model of Alzheimer?s disease[J]. PLoS One, 2012, 7(3):e33312. DOI: 10.1371/journal.pone.0033312 [49] Möhle L, Israel N, Paarmann K, et al.Chronic Toxoplasma gondii infection enhances β-amyloid phagocytosis and clearance by recruited monocytes[J]. Acta Neuropathol Commun, 2016, 4(1):25. DOI: 10.1186/s40478-016-0293-8 [50] Worth AR, Lymbery AJ, Thompson RC.Adaptive host manipulation by Toxoplasma gondii: fact or fiction[J]. Trends Parasitol, 2013, 29(4):150-155. DOI: 10.1016/j.pt.2013.01.004 [51] Gasparotto J, Senger MR, Kunzler A, et al.Increased tau phosphorylation and receptor for advanced glycation end products (RAGE) in the brain of mice infected with Leishmania amazonensis[J]. Brain Behav Immun, 2015, 43:37-45. DOI: 10.1016/j.bbi.2014.06.204 [52] Arancio O, Zhang HP, Chen X, et al.RAGE potentiates A beta-induced perturbation of neuronal function in transgenic mice[J]. EMBO J, 2004, 23(20):4096-4105. DOI: 10.1038/sj.emboj.7600415