Brain-Derived Neurotrophic Factor (BDNF)

Brain-derived neurotrophic factor is a small secreted protein of the nerve growth factor family, made as a precursor and cleaved to a mature dimer. Mature BDNF acts on the receptor tyrosine kinase TrkB, driving signalling that supports neuronal survival, dendritic and axonal growth, and the transcription-dependent late phase of long-term potentiation. The uncleaved precursor, proBDNF, preferentially binds p75NTR and does the opposite, promoting synaptic weakening and apoptosis. Secretion is activity-dependent, and a common human variant at codon 66 reduces that regulated release.

Almost every human number quoted for BDNF is a blood number, and blood is a poor window on brain. Most circulating BDNF is stored in platelets, so serum values, which include what platelets release during clotting, run roughly an order of magnitude above plasma, and both move with platelet count, tourniquet time and clotting protocol. Acute exercise reliably raises circulating BDNF briefly. Correlations between serum and cerebrospinal fluid are weak, and brain tissue cannot be sampled in a living person at all.

That gap is what makes BDNF an exploratory biomarker rather than a surrogate endpoint. A compound that raises serum BDNF has demonstrated an effect on a blood measurement, and nothing further about brain concentrations, synaptic function or cognition follows unless those were measured directly.

Two errors dominate. The first is comparing absolute values across studies when assay, matrix and sample handling differ enough to swamp any treatment effect. The second is the inference chain, standard in supplement marketing, running from a percentage rise in serum BDNF to neurogenesis and then to memory, skipping every step that would have to be shown. Most commercial assays also fail to separate proBDNF from the mature form, which have opposing actions.