Systemic Inflammation and Multimodal Biomarkers in Amnestic Mild Cognitive Impairment and Alzheimer's Disease

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Citações na Scopus
33
Tipo de produção
article
Data de publicação
2018
Título da Revista
ISSN da Revista
Título do Volume
Editora
SPRINGER
Autores
MAGALHAES, T. N. C.
WEILER, M.
TEIXEIRA, C. V. L.
HAYATA, T.
MORAES, A. S.
BOLDRINI, V. O.
SANTOS, L. M. dos
CAMPOS, B. M. de
REZENDE, T. J. R. de
Citação
MOLECULAR NEUROBIOLOGY, v.55, n.7, p.5689-5697, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
There is increasing evidence suggesting that one of the most relevant pathophysiological features of Alzheimer's disease (AD) is neuroinflammation, which plays an important role in the production and regulation of AD-related proteins (amyloid beta (A beta) and Tau) and exacerbates AD pathology. Neuroinflammation can also be induced by systemic influences (factors from outside the central nervous system). However, the role of systemic inflammation in AD pathophysiology is much less understood. Thus, our main objective in this study was to verify whether the presence of serum cytokines (IL-1 beta, IL-6, IL-10, IL-12, and TNF-alpha) affects different AD biomarkers: A beta(1-42) and Tau protein levels, hippocampal volumes (HV), and default mode network functional connectivity (DMN FC) in healthy elderly controls, amnestic mild cognitive impairment (aMCI) patients due to AD, and mild AD patients. To accomplish this, we acquired 3-T MRI, blood, and cerebrospinal fluid (CSF) samples from 42 healthy controls, 55 aMCI patients due to AD, and 33 mild AD patients. Comparing the groups, we found that the mild AD patients presented smaller HV, disrupted DMN FC, and proportionally less IL-1 beta than the controls. The aMCI patients only differed from the controls in DMN FC. In intra-group comparison, aMCI and mild AD with detectable levels of cytokines (TNF-alpha, IL-1 beta, IL-10, and IL-12) had decreased DMN FC. On the other hand, patients with detectable levels of IL-10 and IL-12 presented a more favorable AD biomarkers profile (larger HV, more CSF A beta(1-42), and less p-Tau), indicating a possible protective role of these ILs. Our findings indicate a possible relationship between systemic inflammation with DMN FC disruption, hippocampal atrophy, and CSF protein levels in the subjects with mild AD and aMCI.
Palavras-chave
Systemic inflammation, Alzheimer's disease biomarkers, Functional connectivity, Cytokines, Hippocampal volume, Default mode network
Referências
  1. Agosta F, 2012, NEUROBIOL AGING, V33, P1564, DOI 10.1016/j.neurobiolaging.2011.06.007
  2. Albert MS, 2011, ALZHEIMERS DEMENT, V7, P270, DOI 10.1016/j.jalz.2011.03.008
  3. Alcolea D, 2015, NEUROLOGY, V85, P626, DOI 10.1212/WNL.0000000000001859
  4. Azizi G, 2012, IMMUNOPHARM IMMUNOT, V34, P881, DOI 10.3109/08923973.2012.705292
  5. Banks WA, 2010, FORUM NUTR, V63, P102, DOI 10.1159/000264398
  6. Bhamra MS, 2012, ELECTROPHORESIS, V33, P3598, DOI 10.1002/elps.201200161
  7. Blasko I, 1999, FASEB J, V13, P63
  8. Blennow K, 2009, J ALZHEIMERS DIS, V18, P413, DOI 10.3233/JAD-2009-1177
  9. Bossu P, 2008, BRAIN BEHAV IMMUN, V22, P487, DOI 10.1016/j.bbi.2007.10.001
  10. Bozluolcay M, 2016, GERIATR GERONTOL INT, V16, P1161, DOI 10.1111/ggi.12602
  11. Brosseron F, 2014, MOL NEUROBIOL, V50, P534, DOI 10.1007/s12035-014-8657-1
  12. Brucki SMD, 2003, ARQ NEURO-PSIQUIAT, V61, P777, DOI 10.1590/S0004-282X2003000500014
  13. Ching S, 2005, BRAIN BEHAV IMMUN, V19, P127, DOI 10.1016/j.bbi.2004.06.001
  14. Critchley HD, 2013, NEURON, V77, P624, DOI 10.1016/j.neuron.2013.02.008
  15. Cunningham C, 2015, ALZHEIMERS RES THER, V7, DOI 10.1186/s13195-015-0117-2
  16. Das S, 2008, J NEUROSCI RES, V86, P1199, DOI 10.1002/jnr.21585
  17. de Campos BM, 2016, HUM BRAIN MAPP, V37, P3137, DOI 10.1002/hbm.23231
  18. Dev SI, 2017, INT J GERIATR PSYCH, V32, P341, DOI 10.1002/gps.4482
  19. Devanand DP, 2007, NEUROLOGY, V68, P828, DOI 10.1212/01.wnl.0000256697.20968.d7
  20. Di Rosa M, 2006, EUR J NEUROSCI, V23, P2648, DOI 10.1111/j.1460-9568.2006.04780.x
  21. Dugue B, 1996, INT J CLIN LAB RES, V26, P99, DOI 10.1007/BF02592351
  22. Eikelenboom P, 2006, J NEURAL TRANSM, V113, P1685, DOI 10.1007/s00702-006-0575-6
  23. Emerich DF, 2002, EXP NEUROL, V173, P168, DOI 10.1006/exnr.2001.7835
  24. FAZEKAS F, 1987, AM J ROENTGENOL, V149, P351, DOI 10.2214/ajr.149.2.351
  25. Balthazar MLF, 2014, PSYCHIAT RES-NEUROIM, V221, P37, DOI 10.1016/j.pscychresns.2013.10.010
  26. Fischl B, 2002, NEURON, V33, P341, DOI 10.1016/S0896-6273(02)00569-X
  27. FOLSTEIN MF, 1975, J PSYCHIAT RES, V12, P189, DOI 10.1016/0022-3956(75)90026-6
  28. Forlenza Orestes V, 2015, Alzheimers Dement (Amst), V1, P455, DOI 10.1016/j.dadm.2015.09.003
  29. Franceschi C, 2007, MECH AGEING DEV, V128, P92, DOI 10.1016/j.mad.2006.11.016
  30. Gemma C, 2007, REV NEUROSCIENCE, V18, P137
  31. Gianaros PJ, 2015, CURR DIR PSYCHOL SCI, V24, P313, DOI 10.1177/0963721415581476
  32. Giunta B, 2008, J NEUROINFLAMM, V5, DOI 10.1186/1742-2094-5-51
  33. Hachinski V, 2006, STROKE, V37, P2220, DOI 10.1161/01.STR.0000237236.88823.47
  34. Heneka MT, 2007, J NEUROIMMUNOL, V184, P69, DOI 10.1016/j.jneuroim.2006.11.017
  35. Hennessy E, 2017, BRAIN BEHAV IMMUN, V59, P233, DOI 10.1016/j.bbi.2016.09.011
  36. Hennessy E, 2015, J NEUROSCI, V35, P8411, DOI 10.1523/JNEUROSCI.2745-14.2015
  37. Holmes C, 2009, NEUROLOGY, V73, P768, DOI 10.1212/WNL.0b013e3181b6bb95
  38. Huang YD, 2012, CELL, V148, P1204, DOI 10.1016/j.cell.2012.02.040
  39. Johnston H, 2011, BIOCHEM SOC T, V39, P886, DOI 10.1042/BST0390886
  40. Krstic D, 2012, J NEUROINFLAMM, V9, DOI 10.1186/1742-2094-9-151
  41. Kummer MP, 2014, J NEUROSCI, V34, P8845, DOI 10.1523/JNEUROSCI.4027-13.2014
  42. Labrenz F, 2016, BRAIN BEHAV IMMUN, V54, P17, DOI 10.1016/j.bbi.2015.11.010
  43. Liu L, 2014, AGEING RES REV, V15, P6, DOI 10.1016/j.arr.2013.12.007
  44. Ma Xiaojing, 2015, F1000Res, V4, DOI 10.12688/f1000research.7010.1
  45. Marottoli FM, 2017, ASN NEURO, V9, DOI 10.1177/1759091417719201
  46. Marsland AL, 2017, BRAIN BEHAV IMMUN, V62, P162, DOI 10.1016/j.bbi.2017.01.013
  47. McDermott MF, 2001, CELL MOL BIOL, V47, P619
  48. McKhann GM, 2011, ALZHEIMERS DEMENT, V7, P263, DOI 10.1016/j.jalz.2011.03.005
  49. Meyaard L, 1996, J IMMUNOL, V156, P2776
  50. MORRIS JC, 1993, NEUROLOGY, V43, P2412, DOI 10.1212/WNL.43.11.2412-a
  51. Paouri E, 2017, J NEUROSCI, V37, P5155, DOI 10.1523/JNEUROSCI.2484-16.2017
  52. Popp J, 2017, BRAIN BEHAV IMMUN, V62, P203, DOI 10.1016/j.bbi.2017.01.020
  53. Portielje JEA, 2003, CLIN CANCER RES, V9, P76
  54. Rentzos M, 2006, J NEUROL SCI, V249, P110, DOI 10.1016/j.jns.2006.05.063
  55. Rogers J, 2001, NEUROCHEM INT, V39, P333, DOI 10.1016/S0197-0186(01)00040-7
  56. Scheltens P, 2016, LANCET, V388, P505, DOI 10.1016/S0140-6736(15)01124-1
  57. Stoll G, 2000, J NEURAL TRANSM-SUPP, P81
  58. Sudduth TL, 2013, NEUROBIOL AGING, V34, P1051, DOI 10.1016/j.neurobiolaging.2012.09.012
  59. Swardfager W, 2010, BIOL PSYCHIAT, V68, P930, DOI 10.1016/j.biopsych.2010.06.012
  60. Takeda S, 2014, FRONT AGING NEUROSCI, V6, DOI 10.3389/fnagi.2014.00171
  61. Takeuchi E, 2002, LUNG CANCER-J IASLC, V35, P171, DOI 10.1016/S0169-5002(01)00413-5
  62. Tapiola T, 2009, ARCH NEUROL-CHICAGO, V66, P382, DOI 10.1001/archneurol.2008.596
  63. Tarkowski E, 2003, J NEUROL NEUROSUR PS, V74, P1200, DOI 10.1136/jnnp.74.9.1200
  64. Town T, 2002, J NEUROIMMUNOL, V132, P49, DOI 10.1016/S0165-5728(02)00307-7
  65. Wadhwa M, 1998, J IMMUNOL METHODS, V219, P1, DOI 10.1016/S0022-1759(98)00093-3
  66. Weiler Marina, 2014, Brain Connect, V4, P567, DOI 10.1089/brain.2014.0234
  67. Weiler M, 2014, CURR ALZHEIMER RES, V11, P274, DOI 10.2174/1567205011666140131114716
  68. Wyss-Coray T, 2012, CSH PERSPECT MED, V2, DOI 10.1101/cshperspect.a006346
  69. Xia MR, 2014, J ALZHEIMERS DIS, V39, P527, DOI 10.3233/JAD-131583
  70. Zheng H, 2016, ADV EXP MED BIOL, V941, P117, DOI 10.1007/978-94-024-0921-56