Measuring and Validating the Levels of Brain-Derived Neurotrophic Factor in Human Serum

Abstract

Brain-derived neurotrophic factor (BDNF) secreted by neurons is a significant component of synaptic plasticity. In humans, it is also present in blood platelets where it accumulates following its biosynthesis in megakaryocytes. BDNF levels are thus readily detectable in human serum and it has been abundantly speculated that they may somehow serve as an indicator of brain function. However, there is a great deal of uncertainty with regard to the range of BDNF levels that can be considered normal, how stable these values are over time and even whether BDNF levels can be reliably measured in serum. Using monoclonal antibodies and a sandwich ELISA, this study reports on BDNF levels in the serum of 259 volunteers with a mean value of 32.69 ± 8.33 ng/ml (SD). The mean value for the same cohort after 12 months was not significantly different ( N = 226, 32.97 ± 8.36 ng/ml SD, p = 0.19). Power analysis of these values indicates that relatively large cohorts are necessary to identify significant differences, requiring a group size of 60 to detect a 20% change. The levels determined by ELISA could be validated by Western blot analyses using a BDNF monoclonal antibody. While no association was observed with gender, a weak, positive correlation was found with age. The overall conclusions are that BDNF levels can be reliably measured in human serum, that these levels are quite stable over one year, and that comparisons between two populations may only be meaningful if cohorts of sufficient sizes are assembled.

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References 42

1. 1.

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

   Not in our library10.1002/j.1460-2075.1982.tb01207.x

2. 2.

   Brunoni AR, Lopes M, Fregni F (2008 ) A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol 11:1169–1180.

   Not in our library10.1017/s1461145708009309

3. 3.

   Buchman AS, Yu L, Boyle PA, Schneider JA, De Jager PL, Bennett DA (2016 ) Higher brain BDNF gene expression is associated with slower cognitive decline in older adults. Neurology 86:735–741.

   Not in our library10.1212/wnl.0000000000002387

4. 4.

   Butkiewicz AM, Kemona H, Dymicka-Piekarska V, Matowicka-Karna J, Radziwon P, Lipska A (2006 ) Platelet count, mean platelet volume and thrombocytopoietic indices in healthy women and men. Thromb Res 118:199–204.

   Not in our library10.1016/j.thromres.2005.06.021

5. 5.
   Brain-derived Neurotrophic Factor in Megakaryocytes · 2016

   No notice
6. 6.

   Ciammola A, Sassone J, Cannella M, Calza S, Poletti B, Frati L, Squitieri F, Silani V (2007 ) Low brain-derived neurotrophic factor (BDNF) levels in serum of Huntington's disease patients. Am J Med Genet B Neuropsychiatr Genet 144B:574–577.

   Not in our library10.1002/ajmg.b.30501

7. 7.

   Costa A, Peppe A, Carlesimo GA, Zabberoni S, Scalici F, Caltagirone C, Angelucci F (2015 ) Brain-derived neurotrophic factor serum levels correlate with cognitive performance in Parkinson's disease patients with mild cognitive impairment. Front Behav Neurosci 9:253.

   Not in our library10.3389/fnbeh.2015.00253

8. 8.

   Dinoff A, Herrmann N, Swardfager W, Lanctôt KL (2017 ) The effect of acute exercise on blood concentrations of brain-derived neurotrophic factor in healthy adults: a meta-analysis. Eur J Neurosci 46:1635–1646.

   Not in our library10.1111/ejn.13603

9. 9.

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

   Not in our library10.3109/15622971003797241

10. 10.

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

    Not in our library

11. 11.

    Hofer MM, Barde YA (1988 ) Brain-derived neurotrophic factor prevents neuronal death in vivo. Nature 331:261–262.

    Not in our library10.1038/331261a0

12. 12.

    Howells DW, Porritt MJ, Wong JY, Batchelor PE, Kalnins R, Hughes AJ, Donnan GA (2000 ) Reduced BDNF mRNA expression in the Parkinson's disease substantia nigra. Exp Neurol 166:127–135.

    Not in our library10.1006/exnr.2000.7483

13. 13.

    Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry JM (2002 ) Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 109:143–148.

    Not in our library10.1016/s0165-1781(02)00005-7

14. 14.

    Kolbeck R, Bartke I, Eberle W, Barde YA (1999 ) Brain-derived neurotrophic factor levels in the nervous system of wild-type and neurotrophin gene mutant mice. J Neurochem 72:1930–1938.

    Not in our library10.1046/j.1471-4159.1999.0721930.x

15. 15.

    Laske C, Stransky E, Leyhe T, Eschweiler GW, Wittorf A, Richartz E, Bartels M, Buchkremer G, Schott K (2006 ) Stage-dependent BDNF serum concentrations in Alzheimer's disease. J Neural Transm 113:1217–1224.

    Not in our library10.1007/s00702-005-0397-y

16. 16.

    Lee JG, Shin BS, You YS, Kim JE, Yoon SW, Jeon DW, Baek JH, Park SW, Kim YH (2009 ) Decreased serum brain-derived neurotrophic factor levels in elderly korean with dementia. Psychiatry Investig 6:299–305.

    Not in our library10.4306/pi.2009.6.4.299

17. 17.

    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 26:115–123.

    Not in our library10.1016/j.neurobiolaging.2004.03.002

18. 18.

    Maffioletti E, Zanardini R, Gennarelli M, Bocchio-Chiavetto L (2014 ) Influence of clotting duration on brain-derived neurotrophic factor (BDNF) dosage in serum. Biotechniques 57:111–114.

    Not in our library10.2144/000114204

19. 19.

    Matrisciano F, Bonaccorso S, Ricciardi A, Scaccianoce S, Panaccione I, Wang L, Ruberto A, Tatarelli R, Nicoletti F, Girardi P, Shelton RC (2009 ) Changes in BDNF serum levels in patients with major depression disorder (MDD) after 6 months treatment with sertraline, escitalopram, or venlafaxine. J Psychiatr Res 43:247–254.

    Not in our library10.1016/j.jpsychires.2008.03.014

20. 20.

    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 19:791–800.

    Not in our library10.1038/mp.2013.105

21. 21.

    Mori T, Shimizu K, Hayashi M (2003 ) Levels of serum brain-derived neurotrophic factor in primates. Primates 44:167–169.

    Not in our library10.1007/s10329-002-0015-7

22. 22.

    Onen Sertoz O, Tolga Binbay I, Koylu E, Noyan A, Yildirim E, Elbi Mete H (2008 ) The role of BDNF and HPA axis in the neurobiology of burnout syndrome. Prog Neuropsychopharmacol Biol Psychiatry 32:1459–1465.

    Not in our library10.1016/j.pnpbp.2008.05.001

23. 23.

    Pardridge WM, Kang YS, Buciak JL (1994 ) Transport of human recombinant brain-derived neurotrophic factor (BDNF) through the rat blood-brain barrier in vivo using vector-mediated peptide drug delivery. Pharm Res 11:738–746.

    Not in our library10.1023/a:1018940732550

24. 24.
    A method for reproducible measurements of serum BDNF: comparison of the performance of six commercial assays · 2015

    No notice
25. 25.

    Posthuma JJ, van der Meijden PE, Ten Cate H, Spronk HM (2015 ) Short- and Long-term exercise induced alterations in haemostasis: a review of the literature. Blood Rev 29:171–178.

    Not in our library10.1016/j.blre.2014.10.005

26. 26.

    Rojas Vega S, Strüder HK, Vera Wahrmann B, Schmidt A, Bloch W, Hollmann W (2006 ) Acute BDNF and cortisol response to low intensity exercise and following ramp incremental exercise to exhaustion in humans. Brain Res 1121:59–65.

    Not in our library10.1016/j.brainres.2006.08.105

27. 27.

    Scalzo P, Kümmer A, Bretas TL, Cardoso F, Teixeira AL (2010 ) Serum levels of brain-derived neurotrophic factor correlate with motor impairment in Parkinson's disease. J Neurol 257:540–545.

    Not in our library10.1007/s00415-009-5357-2

28. 28.

    Sen S, Duman R, Sanacora G (2008 ) Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry 64:527–532.

    Not in our library10.1016/j.biopsych.2008.05.005

29. 29.

    Serra-Millas M (2016 ) Are the changes in the peripheral brain-derived neurotrophic factor levels due to platelet activation? World J Psychiatry 6:84–101.

    Not in our library10.5498/wjp.v6.i1.84

30. 30.

    Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, Nakazato M, Watanabe H, Shinoda N, Okada S, Iyo M (2003 ) Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry 54:70–75.

    Not in our library10.1016/s0006-3223(03)00181-1

31. 31.

    Stoll P, Plessow A, Bratke K, Virchow JC, Lommatzsch M (2011 ) Differential effect of clopidogrel and aspirin on the release of BDNF from platelets. J Neuroimmunol 238:104–106.

    Not in our library10.1016/j.jneuroim.2011.06.015

32. 32.

    Szuhany KL, Bugatti M, Otto MW (2015 ) A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. J Psychiatr Res 60:56–64.

    Not in our library10.1016/j.jpsychires.2014.10.003

33. 33.

    Tamura S, Suzuki H, Hirowatari Y, Hatase M, Nagasawa A, Matsuno K, Kobayashi S, Moriyama T (2011 ) Release reaction of brain-derived neurotrophic factor (BDNF) through PAR1 activation and its two distinct pools in human platelets. Thromb Res 128:e55–e61.

    Not in our library10.1016/j.thromres.2011.06.002

34. 34.

    Thompson Ray M, Weickert CS, Wyatt E, Webster MJ (2011 ) Decreased BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders. J Psychiatry Neurosci 36:195–203.

    Not in our library10.1503/jpn.100048

35. 35.

    Tsuchimine S, Sugawara N, Ishioka M, Yasui-Furukori N (2014 ) Preanalysis storage conditions influence the measurement of brain-derived neurotrophic factor levels in peripheral blood. Neuropsychobiology 69:83–88.

    Not in our library10.1159/000358061

36. 36.

    Vahlquist B (1950 ) The cause of the sexual differences in erythrocyte hemoglobin and serum iron levels in human adults. Blood 5:874–875.

    Not in our library

37. 37.

    Wang Y, Liu H, Zhang BS, Soares JC, Zhang XY (2016 ) Low BDNF is associated with cognitive impairments in patients with Parkinson's disease. Parkinsonism Relat Disord 29:66–71.

    Not in our library10.1016/j.parkreldis.2016.05.023

38. 38.

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

    Not in our library10.1523/jneurosci.10-11-03469.1990

39. 39.

    Zagrebelsky M, Korte M (2014 ) Form follows function: BDNF and its involvement in sculpting the function and structure of synapses. Neuropharmacology 76:628–638.

    Not in our library10.1016/j.neuropharm.2013.05.029

40. 40.

    Zahavi J, Jones NA, Leyton J, Dubiel M, Kakkar VV (1980 ) Enhanced in vivo platelet “release reaction” in old healthy individuals. Thromb Res 17:329–336.

    Not in our library10.1016/0049-3848(80)90067-5

Cited by papers we hold 1

• Decreased Serum Brain-Derived Neurotrophic Factor (BDNF) Levels in Patients with Alzheimer’s Disease (AD): A Systematic Review and Meta-Analysis · 2019
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