A method for reproducible measurements of serum

Brain-derived neurotrophic factor (BDNF) is a protein encoded by the BDNF gene in humans and is one of the most extensively studied neurotrophins, a family of proteins that support the growth, survival, and differentiation of neurons in the brain. BDNF plays a crucial role in various processes in the central nervous system, including neurogenesis (the formation of new neurons), synaptic plasticity (the ability of synapses to strengthen or weaken over time), and neuronal survival.

Function:

BDNF promotes the growth and maturation of neurons, as well as the maintenance of existing neurons. It is involved in the formation and remodeling of synapses, which are the connections between neurons where information is transmitted.

Distribution:

BDNF is widely distributed throughout the brain, with particularly high levels found in regions such as the hippocampus, cortex, and basal forebrain.

Role in Learning and Memory:

BDNF is critical for various forms of learning and memory. It is involved in synaptic plasticity mechanisms such as long-term potentiation (LTP), which is believed to underlie learning and memory processes.

Neuroprotection:

BDNF has neuroprotective properties, meaning it helps protect neurons from damage or degeneration. It can promote the survival of neurons under conditions of stress or injury.

Implications in Neurological and Psychiatric Disorders:

Dysregulation of BDNF levels or signaling has been implicated in various neurological and psychiatric disorders, including Alzheimer's disease, depression, schizophrenia, and bipolar disorder. Low levels of BDNF have been associated with these conditions, suggesting that enhancing BDNF signaling could be a potential therapeutic strategy.

Regulation:

BDNF expression can be regulated by various factors, including neuronal activity, hormones, and environmental stimuli. Exercise, for example, has been shown to increase BDNF levels in the brain, which may contribute to its beneficial effects on cognitive function and mood.

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.