How can viruses influence the neuroinflammation and neurodegeneration in the aged human brain

Acta Virologica

Volumn 57, Issue 3, 2013, Pages 273-281

  Marosova L ^a   Neradil, P ^a   Zilka N ^a,b  

^a INSTITUTE OF NEUROIMMUNOLOGY   (Slovakia)

^b Axon Neuroscience Forschungs und Entwicklungs GmbH   (Austria)

Author keywords

Alzheimer's disease; Human brain; Neurodegeneration; Parkinson's disease; Viral infection

Indexed keywords

AGED; ARTICLE; BLOOD BRAIN BARRIER; BRAIN; DEGENERATIVE DISEASE; DISEASE ASSOCIATION; GLIA CELL; HUMAN; IMMUNE RESPONSE; IMMUNOPATHOGENESIS; IMMUNOSENESCENCE; IMMUNOSURVEILLANCE; INNATE IMMUNITY; MICROGLIA; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; SENESCENCE; VIRUS; VIRUS IMMUNITY; VIRUS INFECTION; VIRUS LOAD; VIRUS REACTIVATION; AGING; IMMUNOLOGY; PATHOLOGY; PATHOPHYSIOLOGY; VERY ELDERLY; VIROLOGY;

AGED; AGED, 80 AND OVER; AGING; BRAIN; HUMANS; NEURODEGENERATIVE DISEASES; VIRUS DISEASES;

EID: 84891622989     PISSN: 0001723X     EISSN: None     Source Type: Journal    
DOI: 10.4149/av_2013_03_273     Document Type: Article

References (114)

1. Abbott NJ, Rönnbäck L, Hansson E (2006): Astrocyte-endothelial interactions at the blood-brain barrier. Nat. Rev. Neurosci. 7, 41-53. http://dx.doi.org/10.1038/nrn1824
2. Aloisi F (2001): Immune function of microglia. Glia 36, 165-179. http://dx.doi.org/10.1002/glia.1106
3. Alzheimer's Association (2008): 2008 Alzheimer's disease facts and figures. Alzheimers Dement. 4, 110-133. http://dx.doi.org/10.1016/j.jalz.2008.02.005
4. Araque A, Parpura V, Sanzgiri RP, Haydon PG (1998): Glutamate-dependent astrocyte modulation of synaptic transmission between cultured hippocampal neurons. Eur. J. Neuro sci. 10, 2129-2142. http://dx.doi.org/10.1046/j.1460-9568.1998.00221.x
5. Arkwright PD, Abinum M (2008): Recently identified factors predisposing children to infectious diseases. Curr. Opin. Infect. Dis. 21, 217-222. http://dx.doi.org/10.1097/QCO.0b013e3282fa1824
6. Astic L, Saucier D, Coulon P, Lafay F, Flamand A (1993): The CVS strain of rabies virus as transneuronal tracer in the olfactory system of mice. Brain Res. 619, 146-156. http://dx.doi.org/10.1016/0006-8993(93)91606-S
7. Avramopoulos D, Szymanski M, Wang R, Bassett S (2011): Gene expression reveals overlap between normal aging and Alzheimer's disease genes. Neurobiol. Aging 32, 2319. e27-2319.e34.
8. Baba M, Nakajo S, Tu PH, Tomita T, Nakaya K, Lee VMY, Trojanowski JQ, Iwatsubo T (1998): Aggregation of α-Synuclein in lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies. Am. J. Pathol. 152, 879-884.
9. Ball M (1982): Limbic predilection in Alzheimer dementia: is reactivated herpesvirus involved? Can. J. Neurol. Sci. 9, 303-306.
10. Bitzer-Quintero OK, González-Burgos I (2012): Immune system in the brain: A modulatory role on dendritic spine morphophysiology. Neural. Plast. 2012, 348642. http://dx.doi.org/10.1155/2012/348642
11. Braak H, Braak E (1991): Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 82, 239-259. http://dx.doi.org/10.1007/BF00308809
12. Bradbury MWB (1985): The blood-brain barrier. Transport across the cerebral endothelium. Circ. Res. 57, 213-222. http://dx.doi.org/10.1161/01.RES.57.2.213
13. Brun A (1987): Frontal lobe degeneration of non-Alzheimer type. I. Neuropathology. Arch. Gerontol. Geriatr. 6, 193-208. http://dx.doi.org/10.1016/0167-4943(87)90021-5
14. Buenz EJ, Rodriguez M, Howe CL (2006): Disrupted spatial memory is a consequence of picornavirus infection. Neurobiol. Dis. 24, 266-273. http://dx.doi.org/10.1016/j.nbd.2006.07.003
15. Burgos JS, Ramirez C, Sastre I, Valdivieso F (2006): Effect of apolipoprotein E on the cerebral load of latent herpes simplex virus type 1 DNA. J. Virol. 80, 5383-5387. http://dx.doi.org/10.1128/JVI.00006-06
16. Cairns NJ, Bigio EH, Mackenzie IRA, Neumann M, Lee VMY, Hatanpaa KJ, White III, CL, Schneider JA, Grinberg LT, Halliday G, Duyckaerts C, Lowe JS, Holm IE, Tolnay M, Okamoto K, Yokoo H, Murayama S, Woulfe J, Munoz DG, Dickson DW, Ince PG, Trojanowski JQ, Mann DMA (2007): Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for frontotemporal lobar degeneration. Acta Neuropathol. 114, 1-32. http://dx.doi.org/10.1007/s00401-007-0237-2
17. Compston JE (2002): Bone marrow and bone: a functional unit. J. Endocrinol. 173, 387-394. http://dx.doi.org/10.1677/joe.0.1730387
18. de Bakker PI, Telenti A (2010): Infectious diseases not immune to genome-wide association. Nat. Genet. 42, 731-732. http://dx.doi.org/10.1038/ng0910-731
19. de Lau LML, Breteler MMB (2006): Epidemiology of Parkinson's disease. Lancet Neurol. 5, 525-535. http://dx.doi.org/10.1016/S1474-4422(06)70471-9
20. Dickson DW, Farlo J, Davies P, Crystal H, Fuld P, Yen SHC (1988): Alzheimer's disease. A double-labeling immunohistochemical study of senile plaques. Am. J. Pathol. 132, 86-101.
21. DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N (1997): Aggregation of huntigtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277, 1990-1993. http://dx.doi.org/10.1126/science.277.5334.1990
22. Doherty PC, Zinkernagel RM (1974): T-cell mediated immunopathology in viral infections. Transplant. Rev. 19, 89-120.
23. Eng LF, Ghirnikar RS, Lee YL (2000): Glial fibrillary acidic protein: GFAP-thirty-one years (1969-2000). Neurochem. Res. 25, 1439-1451. http://dx.doi.org/10.1023/A:1007677003387
24. Evans DA, Funkenstein HH, Albert MS, Scherr PA, Cook NR, Chown MJ, Hebert LE, Hennekens CH, Taylor JO (1989): Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported. JAMA 262, 2551-2556. http://dx.doi.org/10.1001/jama.1989.03430180093036
25. Farkas E, Luiten PGM (2001): Cerebral microvascular pathology in aging and Alzheimer's disease. Prog. Neurobiol. 64, 575-611. http://dx.doi.org/10.1016/S0301-0082(00)00068-X
26. Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M, (2005): Global prevalence of dementia: a Delphi consensus study. Lancet 366, 2112-2117. http://dx.doi.org/10.1016/S0140-6736(05)67889-0
27. Franceschi C, Bonafè M, Valensin S (2000): Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space. Vaccine 18, 1717-1720. http://dx.doi.org/10.1016/S0264-410X(99)00513-7
28. Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panagiota Panourgia M, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S (2007): Inflammaging and anti-inflammaging: A systemic perspective on aging and longevity emerged from studies in humans. Mech. Ageing Dev. 128, 92-105. http://dx.doi.org/10.1016/j.mad.2006.11.016
29. Frohman EM, Frohman TC, Dustin ML, Vayuvegula B, Choi B, Gupta A, van den Noort S, Gupta S (1989): The induction of intracellular adhesion molecule 1 (ICAM-1) expression on human fetal astrocytes by interferon-gamma, tumor necrosis factor alpha, lymphotoxin, and interleukin-1: relevance to intracerebral antigen presentation. J. Neuroimmunol. 23, 117-124. http://dx.doi.org/10.1016/0165-5728(89)90030-1
30. Gilden DH, Mahalingam R, Cohrs RJ, Tyler KL (2007): Herpesvirus infections of the nervous system. Nat. Clin. Pract. Neurol. 3, 82-94. http://dx.doi.org/10.1038/ncpneuro0401
31. Goedert M, Spillantini MG, Serpell LC, Berriman J, Smith MJ, Jakes R, Crowther RA (2001): From genetics to pathology: tau and α-synuclein assemblies in neurodegenerative diseases. Phil. Trans. R. Soc. Lond. B. 356, 213-227. http://dx.doi.org/10.1098/rstb.2000.0767
32. Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A (1988): Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: Identification as the microtubule-associated protein tau. Proc. Natl. Acad. Sci. USA 85, 4051-4055. http://dx.doi.org/10.1073/pnas.85.11.4051
33. Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI (1986): Abnormal phosphorylation of the microtubule-associated protein τ (tau) in Alzheimer cytoskeletal pathology. Proc. Natl. Acad. Sci. USA 83, 4913-4917. http://dx.doi.org/10.1073/pnas.83.13.4913
34. Hansen LA, Armstrong DM, Terry RD (1987): An immunohistochemical quantification of fibrous astrocytes in the aging human cerebral cortex. Neurobiol. Aging 8, 1-6. http://dx.doi.org/10.1016/0197-4580(87)90051-0
35. Hardy J, Allsop D (1991): Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol. Sci. 12, 383-388. http://dx.doi.org/10.1016/0165-6147(91)90609-V
36. Hawkins BT, Davis TP (2005): The blood-brain barrier/neurovascular unit in health and disease. Pharmacol. Rev. 57, 173-185. http://dx.doi.org/10.1124/pr.57.2.4
37. Heinz FX, Stiasny K (2012): Flaviviruses and flavivirus vaccines. Vaccine 30, 4301-4306. http://dx.doi.org/10.1016/j.vaccine.2011.09.114
38. Heneka MT, Rodríguez JJ, Verkhratsky A (2010): Neuroglia in neurodegeneration. Brain Res. Rev. 63, 189-211. http://dx.doi.org/10.1016/j.brainresrev.2009.11.004
39. Hokezu Y, Hashiguchi Y, Satake M, Hosoya M (2004): A case report of recurrent limbic encephalitis caused by an enterovirus infection. Rinsho Shinkeigaku 44, 165-170.
40. Hou J, Major EO (2000): Progressive multifocal leukoencephalopathy: JC virus induced demyelination in the immune compromised host. J. Neurovirol. 6, 98-100.
41. Itzhaki RF, Lin WR, Shang D, Wilcock GK, Faragher B, Jamieson, GA (1997): Herpes simplex virus type 1 in brain and risk of Alzheimer's disease. Lancet 349, 241-244. http://dx.doi.org/10.1016/S0140-6736(96)10149-5
42. Jackson AC (2003): Rabies virus infection: an update. J. Neuro. Virol. 9, 253-258.
43. Jamieson GA, Maitland NJ, Wilcock GK, Craske J, Itzhaki RF (1991): Latent herpes simplex virus type 1 in normal and Alzheimer's disease brains. J. Med. Virol. 33, 224-227. http://dx.doi.org/10.1002/jmv.1890330403
44. Jamieson GA, Maitland NJ, Wilcock GK, Yates CM, Itzhaki RF (1992): Herpes simplex virus type 1 DNA is present in specific regions of brain from aged people with and without senile dementia of the Alzheimer type. J. Pathol. 167, 365-368. http://dx.doi.org/10.1002/path.1711670403
45. Johnson RT (1998): Viral infections of the nervous system. 2nd ed. Lippincot-Raven Publishers, Philadelphia.
46. Kagi D, Ledermann B, Burki K, Zinkernagel RM, Hengartner H (1996): Molecular mechanisms of lymphocyte-mediated cytotoxicity and their role in immunological protection and pathogenesis in vivo. Ann. Rev. Immunol. 14, 207-232. http://dx.doi.org/10.1146/annurev.immunol.14.1.207
47. Kreutzberg GW (1996): Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 19, 312-318. http://dx.doi.org/10.1016/0166-2236(96)10049-7
48. Kuno R, Yoshida Y, Nitta A, Nabeshima T, Wang J, Sonobe Y, Kawanokuchi J, Takeuchi H, Mizuno T, Suzumura A (2006): The role of TNF-alpha and its receptors in the production of NGF and GDNF by astrocytes. Brain Res. 1116, 12-18. http://dx.doi.org/10.1016/j.brainres.2006.07.120
49. Kuzis K, Reed S, Cherry NJ, Woodward WR, Eckenstein FP (1995): Developmental time course of acidic and basic fibroblast growth factors' expression in distinct cellular populations of the rat central nervou system. J. Comp. Neurol. 358, 142-153. http://dx.doi.org/10.1002/cne.903580109
50. Lafay F, Coulon P, Astic L, Saucier D, Riche D, Holley A, Flamand A (1991): Spread of the CVS strain of rabies virus and of the avirulent mutant AvO1 along the olfactory pathways of the mouse after intranasal inoculation. Virology 183, 320-330. http://dx.doi.org/10.1016/0042-6822(91)90145-2
51. Lazuardi L, Jenewein B, Wolf AM, Pfister G, Tzankov A, Grubeck-Loebenstein B (2005): Age-related loss of naïve T cells and dysregulation of T-cell/B-cell interactions in human lymph nodes. Immunology 114, 37-43. http://dx.doi.org/10.1111/j.1365-2567.2004.02006.x
52. Leboreiro-Fernandez A, Moura-Ribeiro MVL, Leboreiro IEF, Sawan FM, Ribeiro Ventura A, Kamimura Barbosa KC (1997): Mumps meningoencephalitis. An epidemiological aproach. Arq. Neuropsiquiatr. 55, 12-15. http://dx.doi.org/10.1590/S0004-282X1997000100003
53. Lin WR, Wozniak MA, Cooper RJ, Wilcock GK, Itzhaki RF (2002): Herpesviruses in brain and Alzheimer's disease. J. Pathol. 197, 395-402. http://dx.doi.org/10.1002/path.1127
54. Liow K, Spanaki MV, Boyer RS, Greenlee JE, Bale JF (1999): Bilateral hippocampal encephalitis caused by enteroviral infection. Pediatr. Neurol. 21, 836-838. http://dx.doi.org/10.1016/S0887-8994(99)00083-1
55. Lynch AM, Murphy KJ, Deighan BF, O'Reilly JA, Gun'ko YK, Cowley TR, Gonzalez-Reyes RE, Lynch MA (2010): The impact of glial activation in the aging brain. Aging and Disease 1, 262-278.
56. McCullers JA, Lakeman FD, Whitley RJ (1995): Human herpesvirus 6 is associated with focal encephalitis. Clin. Infect. Dis. 21, 571-576. http://dx.doi.org/10.1093/clinids/21.3.571
57. McGavern DB, Homann D, Oldstone MB (2002): T cell in the central nervous system: the delicate balance between viral clearance and disease. J. Infect. Dis. 186, 45-51. http://dx.doi.org/10.1086/344264
58. McGeer PL, Itagaki S, Boyes BE, McGeer EG (1988): Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology 38, 1285-1291. http://dx.doi.org/10.1212/WNL.38.8.1285
59. McGeer PL, McGeer EG (1995): The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res. Rev. 21, 195-218. http://dx.doi.org/10.1016/0165-0173(95)00011-9
60. Meier JL, Straus SE (1992): Comparative biology of latent varicella-zoster virus and herpes simplex virus infections. J. Infect. Dis. 166, 13-23. http://dx.doi.org/10.1093/infdis/166.Supplement_1.S13
61. Melnick R (1996): Enteroviruses: polioviruses, coxsackieviruses, echoviruses and newer enteroviruses. In Fields BN, Knipe DM, Howley PM, Chanock RM, Monath TP, Melnick JL, Roizman B, Strauss SE: Fields Virology. 3th ed. Lippincott-Raven Publishers, Philadelphia, pp. 655-712.
62. Miller C, Kelsoe G (1995): Ig VH hypermutation is absent in the germinal centers of aged mice. J. Immunol. 155, 3377-3384.
63. Mogi M, Harada M, Kondo T, Riederer P, Inagaki H, Minami M, Nagatsu T (1994a): Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor- alpha are elevated in the brain from parkinsonian patients. Neurosci. Lett. 180, 147-150. http://dx.doi.org/10.1016/0304-3940(94)90508-8
64. Mogi M, Harada M, Riederer P, Narabayashi H, Fujita K, Nagatsu T (1994b): Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci. Lett. 165, 208-210. http://dx.doi.org/10.1016/0304-3940(94)90746-3
65. Mori I, Nishiyama Y, Yokochi T, Kimura Y (2005): Olfactory transmission of neurotropic viruses. J. Neurovirol. 11, 129-137. http://dx.doi.org/10.1080/13550280590922793
66. Mrak RE, Griffin WST (2001): Interleukin-1, neuroinflammation, and Alzheimer's disease. Neurobiol. Aging 22, 903-908. http://dx.doi.org/10.1016/S0197-4580(01)00287-1
67. Mrak RE, Griffin WST (2005): Glia and their cytokines in progression of neurodegeneration. Neurobiol. Aging 26, 349-354. http://dx.doi.org/10.1016/j.neurobiolaging.2004.05.010
68. Mueller NH, Gilden DH, Cohrs RJ, Mahalingam R, Nagel MA (2008): Varicella zoster virus infection: clinical features, molecular pathogenesis of disease, and latency. Neurol. Clin. 26, 1-21. http://dx.doi.org/10.1016/j.ncl.2008.03.011
69. Naylor K, Li G, Vallejo AN, Lee WW, Koetz K, Bryl E, Witkowski J, Fulbright J, Weyand CM, Goronzy JJ (2005): The influence of age on T cell generation and TCR diversity. J. Immunol. 174, 7446-7452.
70. Novak M (1994): Truncated tau protein as a new marker for Alzheimer's disease. Acta Virol. 38, 173-189.
71. Novak M, Jakes R, Edwards PC, Milstein C, Wischik CM (1991): Difference between the tau protein of Alzheimer paired helical filament core and normal tau revealed by epitope analysis of monoclonal antibodies 423 and 7.51. Proc. Natl. Acad. Sci. USA 88, 5837-5841. http://dx.doi.org/10.1073/pnas.88.13.5837
72. Novak M, Kabat J, Wischik CM (1993): Molecular characterization of the minimal protease resistant tau unit of the Alzheimer's disease paired helical filament. EMBO J. 12, 365-370.
73. Oglesbee M, Niewiesk S (2011): Measles virus neurovirulence and host immunity. Future Virol. 6, 85-99. http://dx.doi.org/10.2217/fvl.10.70
74. Pekny M, Nilsson M (2005): Astrocyte activation and reactive gliosis. Glia 50, 427-434. http://dx.doi.org/10.1002/glia.20207
75. Phowthongkum P, Phantumchinda K, Jutivorakool K, Suankratay C (2007): Basal ganglia and brainstem encephalitis, optic neuritis, and radiculomyelitis in Epstein-Barr virus infection. J. Infection. 54, e141-e144. http://dx.doi.org/10.1016/j.jinf.2006.09.007
76. Rock RB, Gekker G, Hu S, Sheng WS, Cheeran M, Lokensgard JR, Peterson PK (2004): Role of microglia in central nervous system infections. Clin. Microbiol. Rev. 17, 942-964. http://dx.doi.org/10.1128/CMR.17.4.942-964.2004
77. Rohn TT, Catlin LW (2011): Immunolocalization of Influenza A virus and markers of inflammation in the human Parkinson's disease brain. PloS ONE 6, e20495. http://dx.doi.org/10.1371/journal.pone.0020495
78. Rotbart HA (2000): Viral meningitis. Semin. Neurol. 20, 277-292. http://dx.doi.org/10.1055/s-2000-9427
79. Sapp E, Kegel KB, Aronin N, Hashikawa T, Uchiyama Y, Tohyama K, Bhide PG, Vonsattel JP, Di Figlia M (2001): Early and progressive accumulation of reactive microglia in the Huntington disease brain. J. Neuropathol. Exp. Neurol. 60, 161-172.
80. Saule P, Trauet J, Dutriez V, Lekeux V, Dessaint JP, Labalette M (2006): Accumulation of memory T cells from childhood to old age: central and effector memory cells in CD4(+) versus effector memory and terminally differentiated memory cells in CD8(+) compartment. Mech. Ageing. Dev. 127, 274-281. http://dx.doi.org/10.1016/j.mad.2005.11.001
81. Selkoe DJ (2004): Cell biology of protein misfolding: The examples of Alzheimer's and Parkinson's diseases. Nat. Cell. Biol. 6, 1054-1061. http://dx.doi.org/10.1038/ncb1104-1054
82. Selkoe DJ, Berman Podlisny M, Joachim CL, Vickers EA, Lee G, Fritz LC, Oltersdorf T (1988): β-Amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues. Proc. Natl. Acad. Sci. USA 85, 7341-7345. http://dx.doi.org/10.1073/pnas.85.19.7341
83. Schneider-Schaulies J, Niewiesk S, Schneider-Schaulies S, ter Meulen V (1999): Measles virus in the CNS: the role of viral and host factors for the establishment and maintenance of a persistent infection. J. Neurovirol. 5, 613-622.http://dx.doi.org/10.3109/13550289909021290
84. Schweinghardt B, Astwood WJ (2001): Virus receptors in the human central nervous system. J. Neurovirol. 7, 187-195. http://dx.doi.org/10.1080/13550280152403236
85. Sheng JG, Mrak RE, Griffin WST (1998): Enlarged and phagocytic, but not primed, interleukin-1α-immunoreactive microglia increase with age in normal human brain. Acta Neuropathol. 95, 229-234.http://dx.doi.org/10.1007/s004010050792
86. Singhrao SK, Neal JW, Morgan BP, Gasque P (1999): Increased complement biosynthesis by microglia and comple ment activation on neurons in Huntington's disease. Exp. Neurol. 159, 362-376.http://dx.doi.org/10.1006/exnr.1999.7170
87. Sokolov VV, Kaplunova OA, Ovseenko TE (2003): Age factors in architectonics of the splenic arterial vessels. Morfologiia 124, 57-60.
88. Sparkman NL, Johnson RW (2008): Neuroinflammation associated with aging sensitizes the brain to the effects of infection or stress. Neuroimmunomodulation 15, 323-330. http://dx.doi.org/10.1159/000156474
89. Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998): α-synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies. Proc. Natl. Acad. Sci. USA 95, 6469-6473. http://dx.doi.org/10.1073/pnas.95.11.6469
90. Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997): Alpha-synuclein in Lewy bodies. Nature 388, 839-840.http://dx.doi.org/10.1038/42166
91. Steiner I, Kennedy PGE, Pachner AR (2007): The neurotropic herpes viruses: herpes simplex and varicella-zoster. Lancet Neurol. 6, 1015-1028. http://dx.doi.org/10.1016/S1474-4422(07)70267-3
92. Steinmann GG (1986): Changes in the human thymus during aging. Curr. Top. Pathol. 75, 43-88. http://dx.doi.org/10.1007/978-3-642-82480-7_2
93. Steinmann GG, Klaus B, Muller-Hermelink HK (1985): The involution of the ageing human thymic epithelium is independent of puberty. A morphometric study. Scand. J. Immunol. 22, 563-575. http://dx.doi.org/10.1111/j.1365-3083.1985.tb01916.x
94. Streit WJ, Braak H, Xue QS, Bechmann I (2009): Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer's disease. Acta Neuropathol. 118, 475-485. http://dx.doi.org/10.1007/s00401-009-0556-6
95. Streit WJ, Kincaid-Colton CA (1995): The brain's immune system. Scientific American 273, 38-43. http://dx.doi.org/10.1038/scientificamerican1195-54
96. Streit WJ, Sammons NW, Kuhns AJ, Sparks DL (2004): Dystrophic microglia in the aging human brain. Glia 45, 208-212. http://dx.doi.org/10.1002/glia.10319
97. Takashima I, Morita K, Chiba M, Hayasaka D, Sato T, Takezawa C, Igarashi A, Kariwa H, Yoshimatsu K, Arikawa J, Hashimoto N (1997): A case of Tick-borne encephalitis in Japan and isolation of the virus. J. Clin. Microbiol. 35, 1943-1947.
98. Tang YW, Shawn Mitchell P, Espy MJ, Smith TF, Persing DH (1999): Molecular diagnosis of herpes simplex virus infections in the central nervous system. J. Clin. Microbiol. 37, 2127-2136.
99. Tang JW, Coward LJ, Davies NWS, Geretti AM, Howard RS, Hirsch NP, Ward KN (2003): Brain stem encephalitis caused by primary herpes simplex 2 infection in a young woman. J. Neurol. Neurosurg. Psychiatry 74, 1323-1325. http://dx.doi.org/10.1136/jnnp.74.9.1323
100. Tebruegge M, Curtis N (2009): Enterovirus infections in neonates. Semin. Fetal Neonatal Med. 14, 222-227. http://dx.doi.org/10.1016/j.siny.2009.02.002
101. The Huntington's disease collaborative research group (1993): A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72, 971-983.
102. Tsutsui Y, Kosugi I, Kawasaki H (2005): Neuropathogenesis in cytomegalovirus infection: Indication of the mechanisms using mouse models. Rev. Med. Virol. 15, 327-345. http://dx.doi.org/10.1002/rmv.475
103. Tuppo EE, Arias HR (2005): The role of inflammation in Alzheimer's disease. Int. J. Biochem. Cell Biol. 37, 289-305. http://dx.doi.org/10.1016/j.biocel.2004.07.009
104. van den Pol AN (2009): Viral infection leading to brain dysfunction: more prevalent than appreciated? Neuron 64, 17-20. http://dx.doi.org/10.1016/j.neuron.2009.09.023
105. Walford RL (1969): The immunologic theory of aging. Copenhagen, Munsksgaard.
106. Weinberger B, Lazuardi L, Weiskirchner I, Keller M, Neuner C, Fischer KH, Neuman B, Wurzner R, Grubeck-Loebenstein B (2007): Healthy aging and latent infection with CMV lead to distinct changes in CD8+ and CD4+ T-cell subsets in the elderly. Hum. Immunol. 68, 86-90. http://dx.doi.org/10.1016/j.humimm.2006.10.019
107. West MJ, Coleman PD, Flood DG, Troncoso JC (1994): Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease. Lancet 344, 769-772. http://dx.doi.org/10.1016/S0140-6736(94)92338-8
108. Wirdefeldt K, Adami HO, Cole P, Trichopoulos D, Mandel J (2011): Epidemiology and etiology of Parkinson's disease: a review of the evidence. Eur. J. Epidemiol. 26, S1-S58. http://dx.doi.org/10.1007/s10654-011-9581-6
109. Wischik CM, Novak M, Edwards PC, Klug A, Tichelaar W, Crowther RA (1988a): Structural characterization of the core of the paired helical filament of Alzheimer disease. Proc. Natl. Acad. Sci. USA 85, 4884-4888. http://dx.doi.org/10.1073/pnas.85.13.4884
110. Wischik CM, Novak M, ThØgersen HC, Edwards PC, Runswick MJ, Jakes R, Walker JE, Milstein C, Roth M, Klug A (1988b): Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease. Proc. Natl. Acad. Sci. USA 85, 4506-4510. http://dx.doi.org/10.1073/pnas.85.12.4506
111. Wolburg H, Lippoldt A (2002): Tight junctions of the blood-brain barrier: development, composition and regulation. Vasc. Pharmacol. 38, 323-337. http://dx.doi.org/10.1016/S1537-1891(02)00200-8
112. Yamada S, Kameyama T, Nagaya S, Hashizume Y, Yoshida M (2003): Relapsing herpes simplex encephalitis: pathological confirmation of viral reactivation. J. Neurol. Neurosurg. Psychiatry 74, 262-264. http://dx.doi.org/10.1136/jnnp.74.2.262
113. Yao K, Honarmand S, Espinoza A, Akhyani N, Glaser C, Jacobson S (2009): Detection of Human herpesvirus-6 in cerebrospinal fluid of patients with encephalitis. Ann. Neurol. 65, 257-267. http://dx.doi.org/10.1002/ana.21611
114. Zhang JR, Tuomanen E (1999): Molecular and cellular mechanisms for microbial entry into the CNS. J. Neurovirol. 5, 591-603. http://dx.doi.org/10.3109/13550289909021288