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 enzyme-linked immunosorbent assay (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. Whilst 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.

Significance Statement The presence of BDNF in human blood has generated considerable interest as illustrated by the very large number of publications associating BDNF levels with various conditions affecting brain function, including depression and neurodegeneration. Yet a range of technical issues, together with a lack of plausible mechanisms explaining this association, raise questions as to the meaning and value of such measurements. This contribution deals with the feasibility of reliably measuring BDNF levels in human serum and gives indications of the size of cohorts to be recruited for meaningful differences to be observed between populations of interest.