A method for reproducible measurements of serum

Brain-derived neurotrophic factor (BDNF) is gaining increasing interest as a potential biomarker to support diagnosis or monitor the effectiveness of therapies in brain disorders. Circulating BDNF can be measured in serum, plasma or whole blood. However, the use of BDNF as a biomarker is limited by the low reproducibility of results, possibly due to the variety of methods used for sample collection and analysis of BDNF.

To overcome these limitations, using sera from 40 healthy adults, we compared the performance of five ELISA kits (Aviscera-Bioscience, Biosensis, Millipore-ChemiKineTM, Promega-Emax®, R&D-System-Quantikine®) and d a multiplexing test (Millipore-Milliplex®). All kits showed 100% sample recovery and comparable range.

However, they showed very different inter-assay variations of 5% to 20%. The inter-assay variations were greater than those declared by the manufacturers with only one exception which also had the best overall performance. Blot analysis revealed that two kits selectively recognized mature BDNF, while the others reacted with both pro-BDNF and mature BDNF. In conclusion, we have identified two assays to obtain reliable measurements of human serum BDNF, suitable for future clinical applications.

The availability of biomarkers to support diagnosis or monitor the efficacy of therapies is a major unmet clinical need in neurology and neuropsychiatry1.

Indeed, despite the large number of published studies on the association between brain disorders and molecular markers present in biological fluids, only a few clinically useful biomarkers have been successfully validated for routine clinical practice2,3,4. Brain-Derived Neurotrophic Factor (BDNF) neurotrophin is one of the most promising biomarkers for brain disorders, but definitive clinical validation is still lacking. BDNF is a secretory dimeric growth factor found in most human tissues, including brain and blood5.

BDNF is known to play a fundamental role in the survival and differentiation of selected neuronal populations during development and in the maintenance and plasticity of neuronal networks in adulthood6,7. Similar to other neurotrophins, BDNF is first synthesized as a precursor protein, called 32 KDa pro-BDNF, which is cleaved by different proteases to produce either the mature 14 KDa form or the truncated by 28 KDa. Interestingly, an altered balance of the different forms has been associated with cognitive impairment and psychiatric disorders