Skip to main content

Advertisement

Log in

Postmortem Brain, Cerebrospinal Fluid, and Blood Neurotrophic Factor Levels in Alzheimer’s Disease: A Systematic Review and Meta-Analysis

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Accumulating evidence suggest that aberrations of neurotrophic factors are involved in the etiology and pathogenesis of Alzheimer’s disease (AD), but clinical data were inconsistent. Therefore, a meta-analysis on neurotrophic factor levels in AD is necessary. We performed a systematic review of blood, CSF, and post-mortem brain neurotrophic factor levels in patients with AD compared with controls and quantitatively summarized the clinical data in blood and CSF with a meta-analytical technique. A systematic search of PubMed and Web of Science identified 98 articles in this study (with samples more than 9000). Random effects meta-analysis demonstrated that peripheral blood BDNF levels were significantly decreased in AD patients compared with controls. However, blood NGF, IGF, and VEGF did not show significant differences between cases and controls. In CSF, random effects meta-analysis showed significantly deceased BDNF and increased NGF levels in patients with AD, whereas IGF and VEGF did not show significant differences between the AD group and control group. In addition, 23 post-mortem studies were included in the systematic review. Although data from post-mortem brains were not always consistent across studies, most studies suggested decreased BDNF and increased (pro)NGF levels in hippocampus and neocortex of patients with AD. These results provide strong clinical evidence that AD is accompanied by an aberrant neurotrophin profile, and future investigations into neurotrophins as biomarkers (especially CSF BDNF and NGF) and therapeutic targets for AD may be warranted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Aisa B, Gil-Bea FJ, Solas M, Garcia-Alloza M, Chen CP, Lai MK et al (2010) Altered NCAM expression associated with the cholinergic system in Alzheimer's disease. J Alzheimers Dis 20(2):659–668

    Article  PubMed  CAS  Google Scholar 

  • Allen SJ, MacGowan SH, Treanor JJ, Feeney R, Wilcock GK, Dawbarn D (1991) Normal beta-NGF content in Alzheimer's disease cerebral cortex and hippocampus. Neurosci Lett 131(1):135–139

    Article  PubMed  CAS  Google Scholar 

  • Almeida RD, Manadas BJ, Melo CV, Gomes JR, Mendes CS, Grãos MM, Carvalho RF, Carvalho AP, Duarte CB (2005) Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways. Cell Death Differ 12(10):1329–1343

    Article  PubMed  CAS  Google Scholar 

  • Angelucci F, Spalletta G, di Iulio F, Ciaramella A, Salani F, Colantoni L, Varsi AE, Gianni W, Sancesario G, Caltagirone C, Bossù P (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  PubMed  CAS  Google Scholar 

  • Arancibia S, Silhol M, Mouliere F et al (2008) Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats. Neurobiol Dis 31(3):316–326

    Article  PubMed  CAS  Google Scholar 

  • Ballatore C, Lee VM, Trojanowski JQ (2007) Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nat Rev Neurosci 8(9):663–672

    Article  PubMed  CAS  Google Scholar 

  • Birks JS, Grimley EJ (2015) Rivastigmine for Alzheimer's disease. Cochrane Database Syst Rev 10(4):CD001191

    Google Scholar 

  • Birks J, Harvey RJ (2006) Donepezil for dementia due to Alzheimer's disease. Cochrane Database Syst Rev 25(1):CD001190

    Google Scholar 

  • Bjorkqvist M, Ohlsson M, Minthon L, Hansson O (2012) Evaluation of a previously suggested plasma biomarker panel to identify Alzheimer's disease. PLoS One 7(1):e29868

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Boutahar N, Reynaud E, Lassabliere F, Borg J (2010) Brain-derived neurotrophic factor inhibits cell cycle reentry but not endoplasmic reticulum stress in cultured neurons following oxidative or excitotoxic stress. J Neurosci Res 88(10):2263–2271

    Article  PubMed  CAS  Google Scholar 

  • Braun DJ, Kalinin S, Feinstein DL (2017) Conditional depletion of hippocampal brain-derived neurotrophic factor exacerbates neuropathology in a mouse model of Alzheimer's disease. ASN Neuro 9(2):1759091417696161

    Article  PubMed  PubMed Central  Google Scholar 

  • Budni J, Bellettini-Santos T, Mina F, Garcez ML, Zugno AI (2015 Sep) The involvement of BDNF, NGF and GDNF in aging and Alzheimer's disease. Aging Dis 6(5):331–341

    Article  PubMed  PubMed Central  Google Scholar 

  • Burns A, Iliffe S (2009) Alzheimer's disease. BMJ 338:b158

    Article  PubMed  Google Scholar 

  • Chang KH, Lyu RK, Ro YS, Chen YC, Ro LS, Chang HS, Huang CC, Liao MF, Wu YR, Kuo HC, Chu CC, Chen CM (2016) Increased serum concentrations of transforming growth factor-beta1 (TGF-beta1) in patients with Guillain-Barre syndrome. Clin Chim Acta 461:8–13

    Article  PubMed  CAS  Google Scholar 

  • Chao MV (2003) Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci 4(4):299–309

    Article  PubMed  CAS  Google Scholar 

  • Cheng Y, Yu LC (2010) Galanin protects amyloid-beta-induced neurotoxicity on primary cultured hippocampal neurons of rats. J Alzheimer's Dis 20(4):1143–1157

    Article  CAS  Google Scholar 

  • Chiappelli M, Borroni B, Archetti S, Calabrese E, Corsi MM, Franceschi M, Padovani A, Licastro F VEGF gene and phenotype relation with Alzheimer's disease and mild cognitive impairment. Rejuvenation Res 2006 Winter;9(4):485–493

  • Connor B, Young D, Yan Q, Faull RL, Synek B, Dragunow M (1997) Brain-derived neurotrophic factor is reduced in Alzheimer's disease. Brain Res Mol Brain Res 49(1-2):71–81

    Article  PubMed  CAS  Google Scholar 

  • Counts SE, He B, Prout JG et al (2016) Cerebrospinal fluid proNGF: a putative biomarker for early Alzheimer's disease. Curr Alzheimer Res 13(7):800–808

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Craig-Schapiro R, Kuhn M, Xiong C, Pickering EH, Liu J, Misko TP, Perrin RJ, Bales KR, Soares H, Fagan AM, Holtzman DM (2011) Multiplexed immunoassay panel identifies novel CSF biomarkers for Alzheimer's disease diagnosis and prognosis. PLoS One 6(4):e18850

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Croll SD, Ransohoff RM, Cai N, Zhang Q, Martin FJ, Wei T, Kasselman LJ, Kintner J, Murphy AJ, Yancopoulos GD, Wiegand SJ (2004) VEGF-mediated inflammation precedes angiogenesis in adult brain. Exp Neurol 187(2):388–402

    Article  PubMed  CAS  Google Scholar 

  • Crutcher KA, Scott SA, Liang S, Everson WV, Weingartner J (1993) Detection of NGF-like activity in human brain tissue: increased levels in Alzheimer's disease. J Neurosci 13(6):2540–2550

    Article  PubMed  CAS  Google Scholar 

  • Durany N, Michel T, Kurt J, Cruz-Sanchez FF, Cervas-Navarro J, Riederer P (2000) Brain-derived neurotrophic factor and neurotrophin-3 levels in Alzheimer's disease brains. Int J Dev Neurosci 18(8):807–813

    Article  CAS  PubMed  Google Scholar 

  • Echeverria V, Barreto GE, Avila-Rodriguez M, Tarasov VV, Aliev G (2017) Is VEGF a key target of cotinine and other potential therapies against Alzheimer disease? Curr Alzheimer Res 14:1155–1163

    Article  PubMed  CAS  Google Scholar 

  • Esposito Z, Belli L, Toniolo S, Sancesario G, Bianconi C, Martorana A (2013) Amyloid beta, glutamate, excitotoxicity in Alzheimer's disease: are we on the right track? CNS Neurosci Ther 19(8):549–555

    Article  PubMed  CAS  Google Scholar 

  • Fahnestock M, Scott SA, Jette N, Weingartner JA, Crutcher KA (1996) Nerve growth factor mRNA and protein levels measured in the same tissue from normal and Alzheimer's disease parietal cortex. Brain Res Mol Brain Res 42(1):175–178

    Article  PubMed  CAS  Google Scholar 

  • Fahnestock M, Michalski B, Xu B, Coughlin MD (2001) The precursor pro-nerve growth factor is the predominant form of nerve growth factor in brain and is increased in Alzheimer's disease. Mol Cell Neurosci 18(2):210–220

    Article  PubMed  CAS  Google Scholar 

  • Faria MC, Goncalves GS, Rocha NP 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 

  • 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  PubMed  CAS  Google Scholar 

  • Forlenza OV, Diniz BS, Teixeira AL, Radanovic M, Talib LL, Rocha NP, Gattaz WF (2015a) Lower cerebrospinal fluid concentration of brain-derived neurotrophic factor predicts progression from mild cognitive impairment to Alzheimer's disease. NeuroMolecular Med 17(3):326–332

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Fujimura H, Altar CA, Chen R, Nakamura T, Nakahashi T, Kambayashi JI, Sun B, Tandon N (2002) Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost 87(4):728–734

    Article  PubMed  CAS  Google Scholar 

  • Gold CA, Budson AE (2008 Dec) Memory loss in Alzheimer's disease: implications for development of therapeutics. Expert Rev Neurother 8(12):1879–1891

    Article  PubMed  PubMed Central  Google Scholar 

  • Gozes I (2017) Specific protein biomarker patterns for Alzheimer's disease: improved diagnostics in progress. EPMA J 8(3):255–259

    Article  PubMed  PubMed Central  Google Scholar 

  • Greenberg ME, Xu B, Lu B, Hempstead BL (2009) New insights in the biology of BDNF synthesis and release: implications in CNS function. J Neurosci 29(41):12764–12767

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Guo J, Wang J, Zhang Z, Yan J, Chen M, Pang T, Zhang L, Liao H (2013) ProNGF inhibits neurogenesis and induces glial activation in adult mouse dentate gyrus. Neurochem Res 38(8):1695–1703

    Article  PubMed  CAS  Google Scholar 

  • Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297(5580):353–356

    Article  PubMed  CAS  Google Scholar 

  • Hellweg R, Gericke CA, Jendroska K, Hartung HD, Cervos-Navarro J (1998) NGF content in the cerebral cortex of non-demented patients with amyloid-plaques and in symptomatic Alzheimer's disease. Int J Dev Neurosci 16(7-8):787–794

    Article  PubMed  CAS  Google Scholar 

  • Hempstead BL (2015) Brain-derived neurotrophic factor: three ligands, many actions. Trans Am Clin Climatol Assoc 126:9–19

    PubMed  PubMed Central  Google Scholar 

  • Hock C, Heese K, Hulette C, Rosenberg C, Otten U (2000) Region-specific neurotrophin imbalances in Alzheimer disease: decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas. Arch Neurol 57(6):846–851

    Article  PubMed  CAS  Google Scholar 

  • Holsinger RM, Schnarr J, Henry P, Castelo VT, Fahnestock M (2000) Quantitation of BDNF mRNA in human parietal cortex by competitive reverse transcription-polymerase chain reaction: decreased levels in Alzheimer's disease. Brain Res Mol Brain Res 76(2):347–354

    Article  PubMed  CAS  Google Scholar 

  • Hu X, Yang Y, Gong D (2016) Circulating insulin-like growth factor 1 and insulin-like growth factor binding protein-3 level in Alzheimer's disease: a meta-analysis, Neurol Sci. 37(10):1671–1677

  • Huang L, Jia J, Liu R (2013) Decreased serum levels of the angiogenic factors VEGF and TGF-beta1 in Alzheimer's disease and amnestic mild cognitive impairment. Neurosci Lett 550:60–63

    Article  PubMed  CAS  Google Scholar 

  • Iulita MF, Cuello AC (2016) The NGF metabolic pathway in the CNS and its dysregulation in down syndrome and Alzheimer's disease. Curr Alzheimer Res 13(1):53–67

    Article  PubMed  CAS  Google Scholar 

  • Jiang C, Salton SR (2013 Mar 01) The role of neurotrophins in major depressive disorder. Transl Neurosci 4(1):46–58

    Article  PubMed  PubMed Central  Google Scholar 

  • Jiang Y, Wei N, Lu T, Zhu J, Xu G, Liu X (2011) Intranasal brain-derived neurotrophic factor protects brain from ischemic insult via modulating local inflammation in rats. Neuroscience 172:398–405

    Article  PubMed  CAS  Google Scholar 

  • Jiao SS, Shen LL, Zhu C, Bu XL, Liu YH, Liu CH et al (2016) Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer's disease. Transl Psychiatry 6(10):e907

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kim YN, Kim DH (2012) Decreased serum angiogenin level in Alzheimer's disease. Prog Neuro-Psychopharmacol Biol Psychiatry 38(2):116–120

    Article  CAS  Google Scholar 

  • Kim BY, Lee SH, Graham PL, Angelucci F, Lucia A, Pareja-Galeano H, Leyhe T, Turana Y, Lee IR, Yoon JH, Shin JI (2017) Peripheral brain-derived neurotrophic factor levels in Alzheimer's disease and mild cognitive impairment: a comprehensive systematic review and meta-analysis. Mol Neurobiol 54(9):7297–7311

    Article  PubMed  CAS  Google Scholar 

  • Laske C, Stellos K, Hoffmann N, Stransky E, Straten G, Eschweiler GW, Leyhe T (2011) Higher BDNF serum levels predict slower cognitive decline in Alzheimer's disease patients. Int J Neuropsychopharmacol 14(3):399–404

    Article  PubMed  CAS  Google Scholar 

  • Lebrun-Julien F, Bertrand MJ, De Backer O et al (2010) ProNGF induces TNFalpha-dependent death of retinal ganglion cells through a p75NTR non-cell-autonomous signaling pathway. Proc Natl Acad Sci U S A 107(8):3817–3822

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee J, Fukumoto H, Orne J, Klucken J, Raju S, Vanderburg CR et al (2005) Decreased levels of BDNF protein in Alzheimer temporal cortex are independent of BDNF polymorphisms. Exp Neurol 194(1):91–96

    Article  PubMed  CAS  Google Scholar 

  • Lee S, Tong M, Hang S, Deochand C, de la Monte S (2013) CSF and brain indices of insulin resistance, oxidative stress and neuro-inflammation in early versus late Alzheimer's disease. J Alzheimers Dis Parkinsonism 3:128

    PubMed  PubMed Central  Google Scholar 

  • Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62(10):e1–e34

    Article  PubMed  Google Scholar 

  • Lu B, Pang PT, Woo NH (2005) The yin and yang of neurotrophin action. Nat Rev Neurosci 6(8):603–614

    Article  PubMed  CAS  Google Scholar 

  • Malishkevich A, Marshall GA, Schultz AP, Sperling RA, Aharon-Peretz J, Gozes I (2016) Blood-borne activity-dependent neuroprotective protein (ADNP) is correlated with premorbid intelligence, clinical stage, and Alzheimer's disease biomarkers. J Alzheimer's Dis 50(1):249–260

    Article  CAS  Google Scholar 

  • Marksteiner J, Pirchl M, Ullrich C, Oberbauer H, Blasko I, Lederer W, Hinterhuber H, Humpel C (2008) Analysis of cerebrospinal fluid of Alzheimer patients. Biomarkers and toxic properties. Pharmacology 82(3):214–220

    Article  PubMed  CAS  Google Scholar 

  • Marksteiner J, Kemmler G, Weiss EM, Knaus G, Ullrich C, Mechtcheriakov S, Oberbauer H, Auffinger S, Hinterhölzl J, Hinterhuber H, Humpel C (2011) Five out of 16 plasma signaling proteins are enhanced in plasma of patients with mild cognitive impairment and Alzheimer's disease. Neurobiol Aging 32(3):539–540

    Article  PubMed  CAS  Google Scholar 

  • Mashayekhi F, Salehin Z (2006) Cerebrospinal fluid nerve growth factor levels in patients with Alzheimer's disease. Ann Saudi Med 26(4):278–282

    Article  PubMed  PubMed Central  Google Scholar 

  • Masi A, Quintana DS, Glozier N, Lloyd AR, Hickie IB, Guastella AJ (2015) Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis. Mol Psychiatry 20(4):440–446

    Article  PubMed  CAS  Google Scholar 

  • Medina M, Avila J (2014) New perspectives on the role of tau in Alzheimer's disease. Implications for therapy. Biochem Pharmacol 88(4):540–547

    Article  PubMed  CAS  Google Scholar 

  • Michalski B, Fahnestock M (2003) Pro-brain-derived neurotrophic factor is decreased in parietal cortex in Alzheimer's disease. Brain Res Mol Brain Res 111(1–2):148–154

    Article  PubMed  CAS  Google Scholar 

  • Michalski B, Corrada MM, Kawas CH, Fahnestock M (2015) Brain-derived neurotrophic factor and TrkB expression in the "oldest-old," the 90+ Study: correlation with cognitive status and levels of soluble amyloid-beta. Neurobiol Aging 36(12):3130–3139

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mor F, Quintana FJ, Cohen IR (2004) Angiogenesis-inflammation cross-talk: vascular endothelial growth factor is secreted by activated T cells and induces Th1 polarization. J Immunol 172(7):4618–4623

    Article  PubMed  CAS  Google Scholar 

  • Mufson EJ, Conner JM, Kordower JH (1995) Nerve growth factor in Alzheimer's disease: defective retrograde transport to nucleus basalis. Neuroreport 6(7):1063–1066

    Article  PubMed  CAS  Google Scholar 

  • Mufson EJ, Ikonomovic MD, Styren SD, Counts SE, Wuu J, Leurgans S et al (2003) Preservation of brain nerve growth factor in mild cognitive impairment and Alzheimer disease. Arch Neurol 60(8):1143–1148

    Article  PubMed  Google Scholar 

  • Mufson EJ, He B, Nadeem M, Perez SE, Counts SE, Leurgans S et al (2012) Hippocampal proNGF signaling pathways and beta-amyloid levels in mild cognitive impairment and Alzheimer disease. J Neuropathol Exp Neurol 71(11):1018–1029

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Nagahara AH, Mateling M, Kovacs I, Wang L, Eggert S, Rockenstein E, Koo EH, Masliah E, Tuszynski MH (2013) Early BDNF treatment ameliorates cell loss in the entorhinal cortex of APP transgenic mice. J Neurosci 33(39):15596–15602

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Narisawa-Saito M, Wakabayashi K, Tsuji S, Takahashi H, Nawa H (1996) Regional specificity of alterations in NGF, BDNF and NT-3 levels in Alzheimer's disease. Neuroreport 7(18):2925–2928

    Article  PubMed  CAS  Google Scholar 

  • Ostrowski PP, Barszczyk A, Forstenpointner J, Zheng W, Feng ZP (2016) Meta-analysis of serum insulin-like growth factor 1 in Alzheimer's disease. PLoS One 11(5):e0155733

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Pedraza CE, Podlesniy P, Vidal N, Arevalo JC, Lee R, Hempstead B et al (2005) Pro-NGF isolated from the human brain affected by Alzheimer's disease induces neuronal apoptosis mediated by p75NTR. Am J Pathol 166(2):533–543

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Peng S, Wuu J, Mufson EJ, Fahnestock M (2004) Increased proNGF levels in subjects with mild cognitive impairment and mild Alzheimer disease. J Neuropathol Exp Neurol 63(6):641–649

    Article  PubMed  CAS  Google Scholar 

  • Peng S, Wuu J, Mufson EJ, Fahnestock M (2005) Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer's disease. J Neurochem 93(6):1412–1421

    Article  PubMed  CAS  Google Scholar 

  • Phillips HS, Hains JM, Armanini M, Laramee GR, Johnson SA, Winslow JW (1991) BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer's disease. Neuron 7(5):695–702

    Article  PubMed  CAS  Google Scholar 

  • Qin XY, Cao C, Cawley NX, Liu TT, Yuan J, Loh YP, Cheng Y (2017a) Decreased peripheral brain-derived neurotrophic factor levels in Alzheimer's disease: a meta-analysis study (N = 7277). Mol Psychiatry 22(2):312–320

    Article  PubMed  CAS  Google Scholar 

  • Qin XY, Wu HT, Cao C, Loh YP, Cheng Y (2017b) A meta-analysis of peripheral blood nerve growth factor levels in patients with schizophrenia. Mol Psychiatry 22(9):1306–1312

    Article  PubMed  CAS  Google Scholar 

  • Querfurth HW, LaFerla FM (2010) Alzheimer's disease. N Engl J Med 362(4):329–344

    Article  PubMed  CAS  Google Scholar 

  • Reitz C (2012) Alzheimer's disease and the amyloid cascade hypothesis: a critical review. Int J Alzheimers Dis 2012:369808

    PubMed  PubMed Central  Google Scholar 

  • Rogers ML, Bailey S, Matusica D, Nicholson I, Muyderman H, Pagadala PC, Neet KE, Zola H, Macardle P, Rush RA (2010) ProNGF mediates death of natural killer cells through activation of the p75NTR-sortilin complex. J Neuroimmunol 226(1–2):93–103

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rubio-Perez JM, Morillas-Ruiz JM (2012) A review: inflammatory process in Alzheimer's disease, role of cytokines. TheScientificWorldJOURNAL 2012:756357

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schaub RT, Anders D, Golz G, Gohringer K, Hellweg R (2002) Serum nerve growth factor concentration and its role in the preclinical stage of dementia. Am J Psychiatry 159(7):1227–1229

    Article  PubMed  Google Scholar 

  • Scott SA, Mufson EJ, Weingartner JA, Skau KA, Crutcher KA (1995) Nerve growth factor in Alzheimer's disease: increased levels throughout the brain coupled with declines in nucleus basalis. J Neurosci 15(9):6213–6221

    Article  PubMed  CAS  Google Scholar 

  • Sofroniew MV, Howe CL, Mobley WC (2001) Nerve growth factor signaling, neuroprotection, and neural repair. Annu Rev Neurosci 24:1217–1281

    Article  PubMed  CAS  Google Scholar 

  • Sragovich S, Merenlender-Wagner A, Gozes I (2017) ADNP plays a key role in autophagy: from autism to schizophrenia and Alzheimer's disease. BioEssays 39(11)

  • Straten G, Eschweiler GW, Maetzler W, Laske C, Leyhe T (2009) Glial cell-line derived neurotrophic factor (GDNF) concentrations in cerebrospinal fluid and serum of patients with early Alzheimer's disease and normal controls. J Alzheimer's Dis 18(2):331–337

    Article  CAS  Google Scholar 

  • Swardfager W, Lanctot K, Rothenburg L, Wong A, Cappell J, Herrmann N (2010) A meta-analysis of cytokines in Alzheimer's disease. Biol Psychiatry 68(10):930–941

    Article  PubMed  CAS  Google Scholar 

  • Tiveron C, Fasulo L, Capsoni S, Malerba F, Marinelli S, Paoletti F, Piccinin S, Scardigli R, Amato G, Brandi R, Capelli P, D'Aguanno S, Florenzano F, la Regina F, Lecci A, Manca A, Meli G, Pistillo L, Berretta N, Nisticò R, Pavone F, Cattaneo A (2013) ProNGF/NGF imbalance triggers learning and memory deficits, neurodegeneration and spontaneous epileptic-like discharges in transgenic mice. Cell Death Differ 20(8):1017–1030

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Todd S, Barr S, Roberts M, Passmore AP (2013) Survival in dementia and predictors of mortality: a review. Int J Geriatr Psychiatry 28(11):1109–1124

    PubMed  Google Scholar 

  • 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(1–3):143–149

    Article  PubMed  CAS  Google Scholar 

  • Wang YJ, Valadares D, Sun Y, Wang X, Zhong JH, Liu XH, Majd S, Chen L, Gao CY, Chen S, Lim Y, Pollard A, Aguilar E, Gai WP, Yang M, Zhou XF (2010) Effects of proNGF on neuronal viability, neurite growth and amyloid-beta metabolism. Neurotox Res 17(3):257–267

    Article  PubMed  CAS  Google Scholar 

  • Wang C, Cui Y, Yang J, Zhang J, Yuan D, Wei Y, Li Y, Duo Y, Li S, Zhu W, Zheng L (2015) Combining serum and urine biomarkers in the early diagnosis of mild cognitive impairment that evolves into Alzheimer's disease in patients with the apolipoprotein E 4 genotype. Biomarkers 20(1):84–88

    Article  PubMed  CAS  Google Scholar 

  • Weinstein G, Beiser AS, Choi SH, Preis SR, Chen TC, Vorgas D, Au R, Pikula A, Wolf PA, DeStefano AL, Vasan RS, Seshadri S (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 

  • Zemva J, Schubert M (2014) The role of neuronal insulin/insulin-like growth factor-1 signaling for the pathogenesis of Alzheimer's disease: possible therapeutic implications. CNS Neurol Disord Drug Targets 13(2):322–337

    Article  PubMed  CAS  Google Scholar 

  • Zetterberg H (2015) Cerebrospinal fluid biomarkers for Alzheimer's disease: current limitations and recent developments. Curr Opin Psychiatry 28(5):402–409

    Article  PubMed  Google Scholar 

  • Zhao Y, Zhao B (2013) Oxidative stress and the pathogenesis of Alzheimer's disease. Oxidative Med Cell Longev 2013:316523

    Google Scholar 

Download references

Acknowledgements

This study was supported by the National Science Foundation of China (81703492), the Beijing Natural Science Foundation (7182092), the Minzu University Research Fund (2018CXTD03), and the MUC 111 project.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yong Cheng.

Ethics declarations

Competing Interests

None declared.

Electronic supplementary material

ESM 1

(PDF 694 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Du, Y., Wu, HT., Qin, XY. et al. Postmortem Brain, Cerebrospinal Fluid, and Blood Neurotrophic Factor Levels in Alzheimer’s Disease: A Systematic Review and Meta-Analysis. J Mol Neurosci 65, 289–300 (2018). https://doi.org/10.1007/s12031-018-1100-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-018-1100-8

Keywords

Navigation