Measurements of brain-derived neurotrophic factor. Methodological aspects and demographical data.

Trajkovska, Viktorija; Marcussen, Anders B.; Vinberg, Maj; Hartvig, Per; Aznar, Susana; Knudsen, Gitte M.

doi:10.1016/j.brainresbull.2007.03.009

Cited by 203Nerve injury and regenerationClinical Laboratory Practices and Quality ControlBiosimilars and Bioanalytical Methods

Measurements of brain-derived neurotrophic factor. Methodological aspects and demographical data.

Trajkovska, Viktorija, Marcussen, Anders B., Vinberg, Maj, Hartvig, Per, Aznar, Susana, Knudsen, Gitte M.·2007·Brain Research Bulletin

DOI 10.1016/j.brainresbull.2007.03.009

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Abstract

Although numerous studies have dealt with changes in blood brain-derived neurotrophic factor (BDNF), methodological issues about BDNF measurements have only been incompletely resolved. We validated BDNF ELISA with respect to accuracy, reproducibility and the effect of storage and repeated freezing cycles on BDNF concentrations. Additionally, the effect of demographic characteristics in healthy subjects on BDNF was verified. Whole blood and serum was collected from 206 healthy subjects and a subgroup was genotyped for BDNF Val66Met polymorphism. The effect of age, gender, BDNF genotype and thrombocyte count on whole blood BDNF was assessed. The BDNF ELISA measurement was accurate, 91.6+/-3.0%, and showed high reproducibility, whereas inter-assay and intra-subject variations were modest, 8.4+/-5.2% and 17.5+/-14.1%, respectively. Storage of whole blood samples at 4 degrees C significantly decreased BDNF concentration, while repeated freezing cycles and storage at -20 degrees C was without any effect. Storage at -20 degrees C of serum, but not whole blood, was associated with a significant decrease in BDNF concentration. Women had significantly higher whole blood BDNF concentrations than men (18.6+/-1.3 ng/ml versus 16.5+/-1.4 ng/ml), and showed a right-skewed BDNF concentration distribution. No association between whole blood BDNF concentrations and thrombocyte count, age, or BDNF genotype was found. In conclusion, the BDNF ELISA assay determines whole blood BDNF accurately and with high reproducibility. Female gender is associated with higher whole blood BDNF concentrations whereas age, thrombocyte count and BDNF Val66Met polymorphism were un-associated.

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BDNF release is influenced by several other non-modifiable factors, such as sex, or non-exercise-related modifiable factors, such as sleep or nutrition, that are known to influence neuroplasticity in general.
“BDNF release is also influenced by several other non-modifiable (e.g., sex Trajkovska et al., 2007; Komulainen et al., 2010; Bus et al., 2011) or non-exercise-related modifiable factors (e.g., sleep or nutrition; Giese et al., 2013, 2014; Walsh et al., 2015; Schmitt et al., 2016) that are known to influence neuroplasticity in general”
From Dose-Response Matters! - A Perspective on the Exercise Prescription in Exercise-Cognition Research (2019) · cites this paper as Trajkovska et al., 2007

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Brain-Derived Neurotrophic Factor in Patients with Huntington's Disease
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Association between Obesity and Circulating Brain-Derived Neurotrophic Factor (BDNF) Levels: Systematic Review of Literature and Meta-Analysis
Sandrini, L., Minno, A. D., Amadio, P., Ieraci, A., Tremoli, E., & Barbieri, S. S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082281 · Cited by 138 · see citing works
Decreased peripheral brain-derived neurotrophic factor levels in Alzheimer’s disease: a meta-analysis study (N=7277)
Qin, X.-Y., Cao, C., Cawley, N. X., Liu, T.-T., Yuan, J., Loh, Y. P., & Cheng, Y. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.62 · Cited by 134 · see citing works
Cardio-respiratory fitness, habitual physical activity and serum brain derived neurotrophic factor (BDNF) in men and women
Currie, J. M. S., Ramsbottom, R., Ludlow, H., Nevill, A. M., & Gilder, M. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.12.043 · Cited by 135 · see citing works
Diurnal Variation of Plasma Brain‐Derived Neurotrophic Factor (BDNF) in Humans: An Analysis of Sex Differences
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The effect of depression, BDNF gene val66met polymorphism and gender on serum BDNF levels
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The impact of childhood abuse and recent stress on serum brain-derived neurotrophic factor and the moderating role of BDNF Val66Met
Elzinga, B. M., Molendijk, M. L., Voshaar, R. C. O., Bus, B. A. A., Prickaerts, J., Spinhoven, P., & Penninx, B. W. J. H. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1961-1 · Cited by 125 · see citing works
High-flavonoid intake induces cognitive improvements linked to changes in serum brain-derived neurotrophic factor: Two randomised, controlled trials
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Molecular mechanisms of brain-derived neurotrophic factor in neuro-protection: Recent developments
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The Center for Integrated Molecular Brain Imaging (Cimbi) database
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Inverse Correlation of Brain and Blood BDNF Levels in a Genetic Rat Model of Depression
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Cognitive and serum BDNF correlates of BDNF Val66Met gene polymorphism in patients with schizophrenia and normal controls
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Acute effects of high-intensity interval training and moderate-intensity continuous exercise on BDNF and irisin levels and neurocognitive performance in late middle-aged and older adults
Tsai, C., Pan, C., Tseng, Y., Chen, F., Chang, Y.-C., & Wang, T.-C. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113472 · Cited by 117 · see citing works
Brain-derived neurotrophic factor (BDNF) and inflammatory markers: Perspectives for the management of depression
Carniel, B. P., & da Rocha, N. S. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110151 · Cited by 116 · see citing works
The Impact of Different Types of Exercise Training on Peripheral Blood Brain-Derived Neurotrophic Factor Concentrations in Older Adults: A Meta-Analysis
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Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression
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Detection of brain-derived neurotrophic factor (BDNF) in rat blood and brain preparations using ELISA: Pitfalls and solutions
Elfving, B., Plougmann, P. H., & Wegener, G. (2010) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2009.12.017 · Cited by 112 · see citing works
Reduced platelet BDNF level in patients with major depression
Lee, B.-H., & Kim, Y.-K. (2009) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.04.002 · Cited by 109 · see citing works
Brain-Derived Neurotrophic Factor (BDNF) in Traumatic Brain Injury–Related Mortality
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Increased serum levels of brain-derived neurotrophic factor in chronic institutionalized patients with schizophrenia
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Plasma BDNF Is Associated with Age-Related White Matter Atrophy but Not with Cognitive Function in Older, Non-Demented Adults
Driscoll, I. F., Martin, B., An, Y., Maudsley, S. R., Ferrucci, L., Mattson, M. P., & Resnick, S. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035217 · Cited by 99 · see citing works
Decreased serum BDNF levels in patients with epileptic and psychogenic nonepileptic seizures
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Brain-Derived Neurotrophic Factor Serum Levels and Genotype: Association with Depression during Interferon-α Treatment
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Daily electronic self-monitoring of subjective and objective symptoms in bipolar disorder—the MONARCA trial protocol (MONitoring, treAtment and pRediCtion of bipolAr disorder episodes): a randomised controlled single-blind trial
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Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker for affective disorders?
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Psychedelics and Neural Plasticity: Therapeutic Implications
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“While molecular changes associated with neuronal plasticity (signaling pathways, gene expression, and protein synthesis) are difficult to assess in vivo in the human brain, BDNF and other plasticity-promoting factors can be measured in serum or whole blood (but not reliably in plasma or CSF) (Trajkovska et al., 2007).”
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A meta-analysis of circulating BDNF concentrations in anorexia nervosa
Brandys, M. K., Kas, M. J., Elburg, A. A. V., Campbell, I. C., & Adan, R. A. H. (2011) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2011.562244 · Cited by 85 · see citing works
Neuroticism, Depressive Symptoms, and Serum BDNF
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Effects of fluoxetine and venlafaxine on serum brain derived neurotrophic factor levels in depressed patients
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Postmortem Brain, Cerebrospinal Fluid, and Blood Neurotrophic Factor Levels in Alzheimer’s Disease: A Systematic Review and Meta-Analysis
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Peripheral Blood Brain-Derived Neurotrophic Factor as a Biomarker of Alzheimer’s Disease: Are There Methodological Biases?
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Genetics of serum BDNF: Meta-analysis of the Val66Met and genome-wide association study
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Dose-and gender-specific effects of resistance training on circulating levels of brain derived neurotrophic factor (BDNF) in community-dwelling older adults
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The brain-derived neurotrophic factor (BDNF) polymorphism Val66Met is associated with neither serum BDNF level nor response to selective serotonin reuptake inhibitors in depressed Japanese patients
Yoshimura, R., Kishi, T., Suzuki, A., Umene‐Nakano, W., Ikenouchi, A., Hori, H., Otani, K., Iwata, N., & Nakamura, J. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2011.02.009 · Cited by 71 · see citing works
BDNF as a biomarker for neuropathic pain: Consideration of mechanisms of action and associated measurement challenges
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Environmental enrichment intervention for Rett syndrome: an individually randomised stepped wedge trial
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Correlation of serum BDNF levels with hippocampal volumes in first episode, medication-free depressed patients
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Phencyclidine (PCP)-Induced Disruption in Cognitive Performance is Gender-Specific and Associated with a Reduction in Brain-Derived Neurotrophic Factor (BDNF) in Specific Regions of the Female Rat Brain
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Diurnal variation and gender differences of plasma brain-derived neurotrophic factor in healthy human subjects
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Changes in plasma and platelet BDNF levels induced by S-citalopram in major depression
Serra-Millàs, M., López-Vílchez, I., Navarro, V., Galán, A.-M., Escolar, G., Penadés, R., Catalán, R., Fañanás, L., Arias, B., & Gastó, C. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2180-0 · Cited by 67 · see citing works
Exploring Serum Levels of Brain Derived Neurotrophic Factor and Nerve Growth Factor Across Glaucoma Stages
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BDNF serum levels, but not BDNF Val66Met genotype, are correlated with personality traits in healthy subjects
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Identification of pro- and mature brain-derived neurotrophic factor in human saliva
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Plasma BDNF concentration, Val66Met genetic variant and depression- related personality traits
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Striatal dopamine transporter binding correlates with serum BDNF levels in patients with striatal dopaminergic neurodegeneration
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Brain-derived neurotrophic factor and its relation to leptin in obese children before and after weight loss
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Tempol and perindopril protect against lipopolysaccharide-induced cognition impairment and amyloidogenesis by modulating brain-derived neurotropic factor, neuroinflammation and oxido-nitrosative stress
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Ketamine Anesthesia Does Not Improve Depression Scores in Electroconvulsive Therapy: A Randomized Clinical Trial
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Brain-derived neurotrophic factor in substance use disorders: A systematic review and meta-analysis
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Sustained effects of single doses of classical psychedelics in humans
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Analysis of serum and plasma identifies differences in molecular coverage, measurement variability, and candidate biomarker selection
Alsaif, M., Guest, P. C., Schwarz, E., Reif, A., Kittel‐Schneider, S., Spain, M., Rahmoune, H., & Bahn, S. (2012) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201100061 · Cited by 54 · see citing works
Peripheral Brain-Derived Neurotrophic Factor Levels in Alzheimer’s Disease and Mild Cognitive Impairment: a Comprehensive Systematic Review and Meta-analysis
Kim, B. Y., Lee, S. H., Graham, P. L., Angelucci, F., Lucía, A., Pareja-Galeano, H., Leyhe, T., Turana, Y., Lee, I. R., Yoon, J. H., et al. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0192-9 · Cited by 56 · see citing works
The BDNF Val66Met polymorphism: Relation to familiar risk of affective disorder, BDNF levels and salivary cortisol
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Serum brain-derived neurotrophic factor and peripheral indicators of the serotonin system in underweight and weight-recovered adolescent girls and women with anorexia nervosa
Ehrlich, S., Salbach‐Andrae, H., Eckart, S., Merle, J. V., Burghardt, R., Pfeiffer, E. F., Franke, L., Uebelhack, R., Lehmkuhl, U., & Hellweg, R. (2009) · Journal of Psychiatry and Neuroscience · doi:10.1139/jpn.0942 · Cited by 54 · see citing works
May BDNF Be Implicated in the Exercise-Mediated Regulation of Inflammation? Critical Review and Synthesis of Evidence
Papathanassoglou, E. D. E., Miltiadous, P., & Karanikola, M. N. K. (2014) · Biological Research For Nursing · doi:10.1177/1099800414555411 · Cited by 53 · see citing works
Stability of BDNF in Human Samples Stored Up to 6 Months and Correlations of Serum and EDTA-Plasma Concentrations
Polyakova, M., Schlögl, H., Sacher, J., Schmidt‐Kassow, M., Kaiser, J., Stümvoll, M., Kratzsch, J., & Schroeter, M. L. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18061189 · Cited by 53 · see citing works
A Critical Evaluation of Wet Biomarkers for Huntington’s Disease: Current Status and Ways Forward
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Serum brain-derived neurotrophic factor, vascular endothelial growth factor and leptin levels in patients with a diagnosis of severe major depressive disorder with melancholic features
Kotan, Z., Sarandöl, E., Kırhan, E., Özkaya, G., & Kırlı, S. (2012) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125312436572 · Cited by 53 · see citing works
Serum brain-derived neurotrophic factor and cognitive functioning in underweight, weight-recovered and partially weight-recovered females with anorexia nervosa
Zwipp, J., Haß, J., Schober, I., Geisler, D., Ritschel, F., Seidel, M., Weiss, J., Roessner, V., Hellweg, R., & Ehrlich, S. (2014) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2014.05.006 · Cited by 48 · see citing works
Expressed Alu repeats as a novel, reliable tool for normalization of real-time quantitative RT-PCR data
Marullo, M., Zuccato, C., Mariotti, C., Lahiri, N., Tabrizi, S. J., Donato, S. D., & Cattaneo, E. F. (2010) · Genome biology · doi:10.1186/gb-2010-11-1-r9 · Cited by 48 · see citing works
Elevated levels of plasma brain derived neurotrophic factor in rapid cycling bipolar disorder patients
Munkholm, K., Pedersen, B. K., Kessing, L. V., & Vinberg, M. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.05.011 · Cited by 48 · see citing works
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Methodological considerations to determine the effect of exercise on brain-derived neurotrophic factor levels
Pareja-Galeano, H., Alis, R., Sanchis‐Gomar, F., Cabo, H., Cortell-Ballester, J., Gómez‐Cabrera, M. C., Lucía, A., & Viña, J. (2014) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2014.11.013 · Cited by 46 · see citing works
Changes in fMRI activation in anterior hippocampus and motor cortex during memory retrieval after an intense exercise intervention
Wagner, G., Herbsleb, M., de la Cruz, F., Schumann, A., Köhler, S., Puta, C., Gabriel, H. W., Reichenbach, J. R., & Bär, K. (2017) · Biological Psychology · doi:10.1016/j.biopsycho.2017.01.003 · Cited by 45 · see citing works
Relationship of circulatory BDNF with cognitive deficits in people with Parkinson's disease
Khalil, H. W., Alomari, M. A., Khabour, O. F., Al-Hieshan, A., & Bajwa, J. A. (2016) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2016.01.032 · Cited by 44 · see citing works
Relevance of Post-Stroke Circulating BDNF Levels as a Prognostic Biomarker of Stroke Outcome. Impact of rt-PA Treatment
Rodier, M., Quirié, A., Prigent‐Tessier, A., Béjot, Y., Jacquin, A., Mossiat, C. M., Marie, C., & Garnier, P. E. (2015) · PLoS ONE · doi:10.1371/journal.pone.0140668 · Cited by 44 · see citing works
Serum brain‐derived neurotrophic factor levels were reduced during methamphetamine early withdrawal
Chen, P., Huang, M., Lai, Y.-C., Chen, P., & Liu, H. (2012) · Addiction Biology · doi:10.1111/j.1369-1600.2012.00444.x · Cited by 43 · see citing works
Hemodialysis Decreases Serum Brain-Derived Neurotrophic Factor Concentration in Humans
Zoladz, J., Śmigielski, M., Majerczak, J., Nowak, Ł. R., Zapart-Bukowska, J., Smoleński, O., Kulpa, J., Duda, K., Drzewińska, J., & Bartosz, G. (2012) · Neurochemical Research · doi:10.1007/s11064-012-0862-6 · Cited by 38 · see citing works
Lack of an association of BDNF Val66Met polymorphism and plasma BDNF with hippocampal volume and memory
Initiative, A. D. N., Kim, A., Fagan, A. M., Goate, A., Benzinger, T. L. S., Morris, J. C., & Head, D. M. (2015) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-015-0343-x · Cited by 41 · see citing works
Measurement Methods of BDNF Levels in Major Depression: A Qualitative Systematic Review of Clinical Trials
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[Letter to the Editor] Influence of Clotting Duration on Brain-Derived Neurotrophic Factor (BDNF) Dosage in Serum
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Effects of lead, mercury, aluminium and manganese co-exposure on the serum BDNF concentration of pre-school children in Taizhou, China
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BDNF Val66Met polymorphism is associated with unstable angina
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Effect of Clotting Duration and Temperature on BDNF Measurement in Human Serum
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Association between reduced serum BDNF levels and insomnia with short sleep duration among female hospital nurses
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Impaired cognition in bipolar I disorder: The roles of the serotonin transporter and brain-derived neurotrophic factor
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Altered levels of brain-derived neurotrophic factor, proBDNF and tissue plasminogen activator in children with posttraumatic stress disorder
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Authors: Trajkovska, V., Marcussen, A. B., Vinberg, M., Hartvig, P., Aznar, S., & Knudsen, G. M.
Affiliations: Copenhagen University Hospital (DK)
Corresponding author: Trajkovska, Viktorija
ORCID: Vinberg, Maj
Aznar, Susana
Knudsen, Gitte M.
Venue: Brain Research Bulletin
Publisher: Elsevier BV
Published: 2007-06
Volume: 73
Issue: 1-3
Pages: 143-149
ISSN: 0361-9230 (ISSN-L)
DOI: 10.1016/j.brainresbull.2007.03.009
OpenAlex: W1969534686
Cited by: 203
References: 50
Citations by year: 2026: 7 · 2025: 4 · 2024: 5 · 2023: 9 · 2022: 7 · 2021: 6 · 2020: 4 · 2019: 12 · 2018: 18 · 2017: 11 · 2016: 13 · 2015: 15 · 2014: 13 · 2013: 10 · 2012: 14
FWCI: 5.43
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Brain Research Bulletin (publishedVersion)
PubMed (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
Keywords: brain-derived neurotrophic factor, sample storage effects, serum BDNF, BDNF Val66Met polymorphism, sex differences, healthy volunteers, platelet count, age effects
MeSH terms: Adult, Aged, Aging, DNA, Enzyme-Linked Immunosorbent Assay, Female, Freezing, Genotype, Humans, Male, Middle Aged, Platelet Count, Polymorphism, Genetic, Reference Standards, Sex Characteristics, Specimen Handling, Reproducibility of Results, Brain-Derived Neurotrophic Factor

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Measurements of brain-derived neurotrophic factor. Methodological aspects and demographical data.

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