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Peripheral Brain-Derived Neurotrophic Factor Levels in Alzheimer’s Disease and Mild Cognitive Impairment: a Comprehensive Systematic Review and Meta-analysis

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Abstract

Alzheimer’s disease (AD) is becoming a growing global problem, and there is an urgent need to identify reliable blood biomarkers of the risk and progression of this condition. A potential candidate is the brain-derived neurotrophic factor (BDNF), which modulates major trophic effects in the brain. However, findings are apparently inconsistent regarding peripheral blood BDNF levels in AD patients vs. healthy people. We thus performed a systematic review and meta-analysis of the studies that have examined peripheral BDNF levels in patients with AD or mild cognitive impairment (MCI) and healthy controls. We searched articles through PubMed, EMBASE, and hand searching. Over a total pool of 2061 potential articles, 26 met all inclusion criteria (including a total of 1584 AD patients, 556 MCI patients, and 1294 controls). A meta-analysis of BDNF levels between early AD and controls showed statistically significantly higher levels (SMD [95 % CI]: 0.72 [0.31, 1.13]) with no heterogeneity. AD patients with a low (<20) mini-mental state examination (MMSE) score had lower peripheral BDNF levels compared with controls (SMD [95 % CI]: −0.33 [−0.60, −0.05]). However, we found no statistically significant difference in blood (serum/plasma) BDNF levels between all AD patients and controls (standard mean difference, SMD [95 % CI]: −0.16 [−0.4, 0.07]), and there was heterogeneity among studies (P < 0.0001, I 2 = 85.8 %). There were no differences in blood BDNF levels among AD or MCI patients vs. controls by subgroup analyses according to age, sex, and drug use. In conclusion, this meta-analysis shows that peripheral blood BDNF levels seem to be increased in early AD and decreased in AD patients with low MMSE scores respectively compared with their age- and sex-matched healthy referents. At present, however, this could not be concluded from individual studies.

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References

  1. Querfurth HW, LaFerla FM (2010) Alzheimer’s disease. N Engl J Med 362:329–344

    Article  CAS  PubMed  Google Scholar 

  2. Ittner LM, Götz J (2011) Amyloid-β and tau—a toxic pas de deux in Alzheimer’s disease. Nat Rev Neurosci 12:65–72

    Article  CAS  PubMed  Google Scholar 

  3. Krstic D, Knuesel I (2013) Deciphering the mechanism underlying late-onset Alzheimer disease. Nat Rev Neurol 9(1):25–34

    Article  CAS  PubMed  Google Scholar 

  4. Tanner CM, Goldman SM, Ross GW, Grate SJ (2014) The disease intersection of susceptibility and exposure: chemical exposures and neurodegenerative disease risk. Alzheimers Dement 10(3):S213–S225

    Article  PubMed  Google Scholar 

  5. Reitz C, Brayne C, Mayeux R (2011) Epidemiology of Alzheimer disease. Nat Rev Neurol 7(3):137–152

    Article  PubMed  PubMed Central  Google Scholar 

  6. Weinstein G, Beiser AS, Choi SH, Preis SR, Chen TC, Vorgas D, Vasan RS (2014) Serum brain-derived neurotrophic factor and the risk for dementia: the Framingham heart study. JAMA Neurol 71(1):55–61

    Article  PubMed  PubMed Central  Google Scholar 

  7. Barde YA, Edgar D, Thoenen H (1982) Purification of a new neurotrophic factor from mammalian brain. The EMBO J 1(5):549–553

    CAS  PubMed  Google Scholar 

  8. Autry AE, Monteggia LM (2012) Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev 64(2):238–258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Nagahara AH, Tuszynski MH (2011) Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov 10(3):209–219

    Article  CAS  PubMed  Google Scholar 

  10. Lu B, Nagappan G, Guan X, Nathan PJ, Wren P (2013) BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases. Nat Rev Neurosci 14(6):401–416

    Article  CAS  PubMed  Google Scholar 

  11. Fernandes BS, Steiner J, Berk M, Molendijk ML, Gonzalez-Pinto A, Turck CW, Gonçalves CA (2015) Peripheral brain-derived neurotrophic factor in schizophrenia and the role of antipsychotics: meta-analysis and implications. Mol Psychiatry 20(9):1108–1119

    Article  CAS  PubMed  Google Scholar 

  12. Munkholm K, Vinberg M, Kessing LV (2015) Peripheral blood brain-derived neurotrophic factor in bipolar disorder: a comprehensive systematic review and meta-analysis. Mol Psychiatry 21(9):216–228

  13. Fernandes BS, Berk M, Turck CW, Steiner J, Goncalves CA (2014) Decreased peripheral brain-derived neurotrophic factor levels are a biomarker of disease activity in major psychiatric disorders: a comparative meta-analysis. Mol Psychiatry 19(7):750​–751

    Article  CAS  PubMed  Google Scholar 

  14. Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ (1998) Transport of brain-derived neurotrophic factor across the blood–brain barrier. Neuropharmacology 37(12):1553–1561

    Article  CAS  PubMed  Google Scholar 

  15. Karege F, Schwald M, Cisse M (2002) Postnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets. Neurosci Lett 328(3):261–264

    Article  CAS  PubMed  Google Scholar 

  16. Pareja-Galeano H, Alis R, Sanchis-Gomar F, Cabo H, Cortell-Ballester J, Gomez-Cabrera MC, Viña J (2015) Methodological considerations to determine the effect of exercise on brain-derived neurotrophic factor levels. Clin Biochem 48(3):162–166

    Article  CAS  PubMed  Google Scholar 

  17. Balaratnasingam S, Janca A (2012) Brain derived neurotrophic factor: a novel neurotrophin involved in psychiatric and neurological disorders. Pharmacol Ther 134(1):116–124

    Article  CAS  PubMed  Google Scholar 

  18. Pliego-Rivero FB, Bayatti N, Giannakoulopoulos X, Glover V, Bradford HF, Stern G, Sandier M (1997) Brain-derived neurotrophic factor in human platelets. Biochem Pharmacol 54(1):207–209

    Article  CAS  PubMed  Google Scholar 

  19. Karege F, Bondolfi G, Gervasoni N, Schwald M, Aubry JM, Bertschy G (2005) Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity. Biol Psychiatry 57(9):1068–1072

    Article  CAS  PubMed  Google Scholar 

  20. Lommatzsch M, Zingler D, Schuhbaeck K, Schloetcke K, Zingler C, Schuff-Werner P, Virchow JC (2005) The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol Aging 26(1):115–123

    Article  CAS  PubMed  Google Scholar 

  21. Ziegenhorn AA, Schulte-Herbrüggen O, Danker-Hopfe H, Malbranc M, Hartung HD, Anders D, Hellweg R (2007) Serum neurotrophins—a study on the time course and influencing factors in a large old age sample. Neurobiol Aging 28(9):1436–1445

    Article  CAS  PubMed  Google Scholar 

  22. Sartorius A, Hellweg R, Litzke J, Vogt M, Dormann C, Vollmayr B, Gass P (2009) Correlations and discrepancies between serum and brain tissue levels of neurotrophins after electroconvulsive treatment in rats. Pharmacopsychiatry 42(06):270–276

    Article  CAS  PubMed  Google Scholar 

  23. Yamada K, Nabeshima T (2003) Brain-derived neurotrophic factor/TrkB signaling in memory processes. J Pharmacol Sci 91(4):267–270

    Article  CAS  PubMed  Google Scholar 

  24. Brandys MK, Kas MJ, van Elburg AA, Campbell IC, Adan RA (2011) A meta-analysis of circulating BDNF concentrations in anorexia nervosa. World J Biol Psychiatry 12(6):444–454

    Article  PubMed  Google Scholar 

  25. Petryshen TL, Sabeti PC, Aldinger KA, Fry B, Fan JB, Schaffner SF, Sklar P (2010) Population genetic study of the brain-derived neurotrophic factor (BDNF) gene. Mol Psychiatry 15(8):810–815

    Article  CAS  PubMed  Google Scholar 

  26. Hashimoto K (2010) Brain-derived neurotrophic factor as a biomarker for mood disorders: an historical overview and future directions. Psychiatry Clin Neurosci 64(4):341–357

    Article  CAS  PubMed  Google Scholar 

  27. Molendijk ML, Spinhoven P, Polak M, Bus BA, Penninx BW, Elzinga BM (2014) Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N = 9484). Mol Psychiatry 19(7):791–800

    Article  CAS  PubMed  Google Scholar 

  28. Forlenza OV, Miranda AS, Guimar I, Talib LL, Diniz BS, Gattaz WF, Teixeira AL (2015) Decreased neurotrophic support is associated with cognitive decline in non-demented subjects. J Alzheimers Dis 46(2):423–429

    Article  CAS  PubMed  Google Scholar 

  29. Passaro A, Dalla Nora E, Morieri ML, Soavi C, Sanz JM, Zurlo A, Zuliani G (2014) Brain-derived neurotrophic factor plasma levels: relationship with dementia and diabetes in the elderly population. J Gerontol A Biol Sci Med Sci 70:294–302

    Article  PubMed  Google Scholar 

  30. Álvarez A, Aleixandre M, Linares C, Masliah E, Moessler H (2014) Apathy and APOE4 are associated with reduced BDNF levels in Alzheimer’s disease. J Alzheimers Dis 42(4):1347–1355

    PubMed  PubMed Central  Google Scholar 

  31. Coelho FG, Vital TM, Stein AM, Arantes FJ, Rueda AV, Camarini R, Santos-Galduroz RF (2014) Acute aerobic exercise increases brain-derived neurotrophic factor levels in elderly with Alzheimer’s disease. J Alzheimers Dis 39(2):401–408

    CAS  PubMed  Google Scholar 

  32. Curto M, Martocchia A, Comite F, Scaccianoce S, Xenos D, Nasca C, Falaschi P (2014) The presence of depressive symptoms in comorbidity with Alzheimer’s disease does not influence changes in serum brain-derived neurotrophic factor levels in older patients. Int J Geriatr Psychiatry 29(4):439–440

    Article  PubMed  Google Scholar 

  33. Diniz BS, Reynolds CF, Begley A, Dew MA, Anderson SJ, Lotrich F, Butters MA (2014) Brain-derived neurotrophic factor levels in late-life depression and comorbid mild cognitive impairment: a longitudinal study. J Psychiatr Res 49:96–101

    Article  PubMed  Google Scholar 

  34. Liu YH, Jiao SS, Wang YR, Bu XL, Yao XQ, Xiang Y, Zhou XF (2015) Associations between ApoEε4 carrier status and serum BDNF levels—new insights into the molecular mechanism of ApoEε4 actions in Alzheimer’s disease. Mol Neurobiol 51(3):1271–1277

    Article  CAS  PubMed  Google Scholar 

  35. Nagata T, Kobayashi N, Shinagawa S, Yamada H, Kondo K, Nakayama K (2014) Plasma BDNF levels are correlated with aggressiveness in patients with amnestic mild cognitive impairment or Alzheimer disease. J Neural Transm 121(4):433–441

    Article  CAS  PubMed  Google Scholar 

  36. Manuela Crispim Nascimento C, Rodrigues Pereira J, Pires de Andrade L, Garuffi M, Leme Talib L, Vicente Forlenza O, Stella F (2014) Physical exercise in MCI elderly promotes reduction of pro-inflammatory cytokines and improvements on cognition and BDNF peripheral levels. Curr Alzheimer Res 11(8):799–805

    Article  Google Scholar 

  37. Turana Y, Ranakusuma TAS, Purba JS, Amir N, Ahmad SA, Machfoed MH, Waspadji S (2014) Enhancing diagnostic accuracy of aMCI in the elderly: combination of olfactory test, pupillary response test, BDNF plasma level, and APOE genotype. Int J Alzheimers Dis 2014:912586. doi:10.1155/2014/912586

  38. Sonali N, Tripathi M, Sagar R, Vivekanandhan S (2013) Val66Met polymorphism and BDNF levels in Alzheimer’s disease patients in north Indian population. Int J Neurosci 123(6):409–416

    Article  CAS  PubMed  Google Scholar 

  39. Ventriglia M, Zanardini R, Bonomini C, Zanetti O, Volpe D, Pasqualetti P et al (2013) Serum brain-derived neurotrophic factor levels in different neurological diseases. Biomed Res Int 2013:901082. doi:10.1155/2013/901082

  40. Konukoglu D, Andican G, Fırtına S, Erkol G, Kurt A (2012) Serum brain-derived neurotrophic factor, nerve growth factor and neurotrophin-3 levels in dementia. Acta Neurol Belg 112(3):255–260

    Article  PubMed  Google Scholar 

  41. O’Bryant SE, Hobson VL, Hall JR, Barber RC, Zhang S, Johnson L et al (2010) Serum brain-derived neurotrophic factor levels are specifically associated with memory performance among Alzheimer’s disease cases. Dement Geriatr Cogn Disord 31(1):31–36

    Article  PubMed  PubMed Central  Google Scholar 

  42. Angelucci F, Spalletta G, Fd I, Ciaramella A, Salani F, Varsi A et al (2010) Alzheimer’s disease (AD) and mild cognitive impairment (MCI) patients are characterized by increased BDNF serum levels. Curr Alzheimer Res 7(1):15–20

    Article  CAS  PubMed  Google Scholar 

  43. Forlenza OV, Diniz BS, Teixeira AL, Ojopi EB, Talib LL, Mendonça VA et al (2010) Effect of brain-derived neurotrophic factor Val66Met polymorphism and serum levels on the progression of mild cognitive impairment. World J Biol Psychiatry 11(6):774–780

    Article  PubMed  Google Scholar 

  44. Leyhe T, Eschweiler GW, Stransky E, Gasser T, Annas P, Basun H et al (2009) Increase of BDNF serum concentration in lithium treated patients with early Alzheimer’s disease. J Alzheimers Dis 16(3):649–656

    Article  CAS  PubMed  Google Scholar 

  45. O’Bryant SE, Hobson V, Hall JR, Waring SC, Chan W, Massman P et al (2009) Brain-derived neurotrophic factor levels in Alzheimer’s disease. J Alzheimers Dis 17(2):337–341

    Article  PubMed  PubMed Central  Google Scholar 

  46. Leyhe T, Stransky E, Eschweiler G, Buchkremer G, Laske C (2008) Increase of BDNF serum concentration during donepezil treatment of patients with early Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 258(2):124–128

    Article  CAS  PubMed  Google Scholar 

  47. Laske C, Stransky E, Leyhe T, Eschweiler G, Wittorf A, Richartz E et al (2006) Stage-dependent BDNF serum concentrations in Alzheimer’s disease. J Neural Transm 113(9):1217–1224

    Article  CAS  PubMed  Google Scholar 

  48. Yasutake C, Kuroda K, Yanagawa T, Okamura T, Yoneda H (2006) Serum BDNF, TNF-α and IL-1β levels in dementia patients. Eur Arch Psychiatry Clin Neurosci 256(7):402–406

    Article  PubMed  Google Scholar 

  49. Faria MC, Gonçalves GS, Rocha NP, Moraes EN, Bicalho MA, Gualberto Cintra MT et al (2014) Increased plasma levels of BDNF and inflammatory markers in Alzheimer’s disease. J Psychiatr Res 53:166–172

    Article  PubMed  Google Scholar 

  50. Yu H, Zhang Z, Shi Y, Bai F, Xie C, Qian Y et al (2008) Association study of the decreased serum BDNF concentrations in amnestic mild cognitive impairment and the Val66Met polymorphism in Chinese Han. J Clin Psychiatry 69(7):1104–1111

    Article  CAS  PubMed  Google Scholar 

  51. Laske C, Stransky E, Leyhe T, Eschweiler GW, Maetzler W, Wittorf A et al (2007) BDNF serum and CSF concentrations in Alzheimer’s disease, normal pressure hydrocephalus and healthy controls. J Psychiatr Res 41(5):387–394

    Article  PubMed  Google Scholar 

  52. Laske C, Stransky E, Leyhe T, Eschweiler GW, Schott K, Langer H et al (2006) Decreased brain-derived neurotrophic factor (BDNF)-and beta-thromboglobulin (beta-TG)-blood levels in Alzheimer’s disease. Thromb Haemost 96(1):102–103

    CAS  PubMed  Google Scholar 

  53. Laske C, Stransky E, Eschweiler GW, Wittorf A, Richartz-Salzburger E, Buchkremer G et al (2005) Correlation of BDNF and IL-6 serum concentrations in Alzheimer’s disease. Neurol Psychiatr Brain Res 12(1):21–24

    Google Scholar 

  54. Gezen-Ak D, Dursun E, Hanağası H, Bilgiç B, Lohman E, Araz ÖS et al (2013) BDNF, TNFα, HSP90, CFH, and IL-10 serum levels in patients with early or late onset Alzheimer’s disease or mild cognitive impairment. J Alzheimers Dis 37(1):185–195

    CAS  PubMed  Google Scholar 

  55. Woolley JD, Strobl EV, Shelly WB, Karydas AM, Robin Ketelle RN, Wolkowitz OM et al (2012) BDNF serum concentrations show no relationship with diagnostic group or medication status in neurodegenerative disease. Curr Alzheimer Res 9(7):815–821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lee JG, Shin BS, You YS, Kim JE, Yoon SW, Jeon DW et al (2009) Decreased serum brain-derived neurotrophic factor levels in elderly Korean with dementia. Psychiatry Investig 6(4):299–305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Pláteník J, Fišar Z, Buchal R, Jirák R, Kitzlerová E, Zvěřová M et al (2014) GSK3β, CREB, and BDNF in peripheral blood of patients with Alzheimer’s disease and depression. Prog Neuro-Psychopharmacol Biol Psychiatry 50:83–93

    Article  Google Scholar 

  58. Laske C, Stransky E, Eschweiler G, Wittorf A, Richartz-Salzburger E, Bartels M et al (2005) BDNF serum concentrations in patients with Alzheimer’s disease are associated with depressive mood states. Neurol Psychiatr Brain Res 12(1):1–4

    Google Scholar 

  59. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E (1999) Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 56(3):303–308

    Article  CAS  PubMed  Google Scholar 

  60. Petersen RC, Parisi JE, Dickson DW, Johnson KA, Knopman DS, Boeve BF et al (2006) Neuropathologic features of amnestic mild cognitive impairment. Arch Neurol 63(5):665–672

    Article  PubMed  Google Scholar 

  61. Schmidtke K, Hermeneit S (2008) High rate of conversion to Alzheimer’s disease in a cohort of amnestic MCI patients. Int Psychogeriatr 20(1):96–108

    Article  PubMed  Google Scholar 

  62. Palmqvist S, Hansson O, Minthon L, Londos E (2009) Practical suggestions on how to differentiate dementia with Lewy bodies from Alzheimer’s disease with common cognitive tests. Int J Geriatr Psychiatry 24(12):1405–1412

    Article  PubMed  Google Scholar 

  63. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535

    Article  PubMed  PubMed Central  Google Scholar 

  64. Higgins JP, Green S (eds) (2013) Cochrane handbook for systematic reviews of interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Wiley-Blackwell, New Jersey. Available from www.handbook.cochrane.org

  65. Durlak JA (2009) How to select, calculate, and interpret effect sizes. J Pediatr Psychol 34:917–928

    Article  PubMed  Google Scholar 

  66. Wan X, Wang W, Liu J, Tong T (2014) Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 14(1):135

    Article  PubMed  PubMed Central  Google Scholar 

  67. Borenstein M, Hedges LV, Higgins JP, Rothstein HR (2010) A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods 1(2):97–111

    Article  PubMed  Google Scholar 

  68. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed  PubMed Central  Google Scholar 

  69. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Duval S, Tweedie R (2000) Trim and fill: a simple funnel-plot–based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56(2):455–463

    Article  CAS  PubMed  Google Scholar 

  71. García-Mesa Y, Pareja-Galeano H, Bonet-Costa V, Revilla S, Gómez-Cabrera MC, Gambini J, Sanfeliu C (2014) Physical exercise neuroprotects ovariectomized 3xTg-AD mice through BDNF mechanisms. Psychoneuroendocrinology 45:154–166

    Article  PubMed  Google Scholar 

  72. Psotta L, Rockahr C, Gruss M, Kirches E, Braun K, Lessmann V, Endres T (2015) Impact of an additional chronic BDNF reduction on learning performance in an Alzheimer mouse model. Front Behav Neurosci 9:58

    Article  PubMed  PubMed Central  Google Scholar 

  73. Nagahara AH, Merrill DA, Coppola G, Tsukada S, Schroeder BE, Shaked GM, Rockenstein E (2009) Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease. Nat Med 15(3):331–337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Zuccato C, Cattaneo E (2009) Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol 5(6):311–322

    Article  CAS  PubMed  Google Scholar 

  75. Cai J, Hua F, Yuan L, Tang W, Lu J, Yu S, Hu Y (2014) Potential therapeutic effects of neurotrophins for acute and chronic neurological diseases. Biomed Res Int 2014:601084. doi:10.1155/2014/601084

  76. Huang TL, Lee CT, Liu YL (2008) Serum brain-derived neurotrophic factor levels in patients with major depression: effects of antidepressants. J Psychiatr Res 42(7):521–525

    Article  PubMed  Google Scholar 

  77. Molendijk ML, Bus BA, Spinhoven P, Penninx BW, Kenis G, Prickaerts J, Elzinga BM et al (2011) Serum levels of brain-derived neurotrophic factor in major depressive disorder: state–trait issues, clinical features and pharmacological treatment. Mol Psychiatry 16(11):1088–1095

    Article  CAS  PubMed  Google Scholar 

  78. Quiroz JA, Machado-Vieira R, Zarate CA Jr, Manji HK (2010) Novel insights into lithium’s mechanism of action: neurotrophic and neuroprotective effects. Neuropsychobiology 62(1):50–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Simmons DA, Rex CS, Palmer L, Pandyarajan V, Fedulov V, Gall CM et al (2009) Up-regulating BDNF with an ampakine rescues synaptic plasticity and memory in Huntington’s disease knockin mice. Proc Natl Acad Sci U S A 106(12):4906–4911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Lee BH, Kim YK (2009) Reduced platelet BDNF level in patients with major depression. Progr Neuro-Psychopharmacol Biol Psychiatry 33(5):849–853

    Article  CAS  Google Scholar 

  81. Yamamoto H, Gurney ME (1990) Human platelets contain brain-derived neurotrophic factor. J Neurosci 10(11):3469–3478

    CAS  PubMed  Google Scholar 

  82. Gass P, Hellweg R (2010) Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker for affective disorders? Int J Neuropsychopharmacology 13(1):1–4

    Article  CAS  Google Scholar 

  83. Trajkovska V, Marcussen AB, Vinberg M, Hartvig P, Aznar S, Knudsen GM (2007) Measurements of brain-derived neurotrophic factor: methodological aspects and demographical data. Brain Res Bull 73(1):143–149

    Article  CAS  PubMed  Google Scholar 

  84. Polacchini A, Metelli G, Francavilla R, Baj G, Florean M, Mascaretti LG, Tongiorgi E (2015) A method for reproducible measurements of serum BDNF: comparison of the performance of six commercial assays. Scientific Reports 5:17989. doi:10.1038/srep17989

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Acknowledgments

We thank the authors of included papers, in particular all of the authors supplying or clarifying the data for the present study. We have no funding relevant to this investigation.

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Authors and Affiliations

  1. College of Medicine, Ewha Womans University, Seoul, South Korea

    Bo Yi Kim & Ji Hye Yoon

  2. Department of Nursing Science, College of Nursing, Gachon University, Incheon, South Korea

    Seon Heui Lee

  3. Department of Statistics, Macquarie University, Sydney, Australia

    Petra L. Graham

  4. Department of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italy

    Francesco Angelucci

  5. Research Institute of Hospital 12 de Octubre (i+12), European University of Madrid, Madrid, Spain

    Alejandro Lucia & Helios Pareja-Galeano

  6. Center of Old Age Psychiatry, Psychiatric University Hospital, Basel, Switzerland

    Thomas Leyhe

  7. Department of Neurology, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia

    Yuda Turana

  8. Department of Pediatrics, Yonsei University College of Medicine, 50 Yonsei-Ro, Seoul, 120-752, Republic of Korea

    I Re Lee & Jae Il Shin

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Kim, B.Y., Lee, S.H., Graham, P.L. et al. Peripheral Brain-Derived Neurotrophic Factor Levels in Alzheimer’s Disease and Mild Cognitive Impairment: a Comprehensive Systematic Review and Meta-analysis. Mol Neurobiol 54, 7297–7311 (2017). https://doi.org/10.1007/s12035-016-0192-9

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