Tissue-Specificity of Antibodies Raised Against TrkB and p75NTR Receptors; Implications for Platelets as Models of Neurodegenerative Diseases

Platelets and neurons share many similarities including comparable secretory granule types with homologous calcium-dependent secretory mechanisms as well as internalization, sequestration and secretion of many neurotransmitters. Thus, platelets present a high potential to be used as peripheral biomarkers to reflect neuronal pathologies. The brain-derived neurotrophic factor (BDNF) acts as a neuronal growth factor involved in learning and memory through the binding of two receptors, the tropomyosin receptor kinase B (TrkB) and the 75 kDa pan-neurotrophic receptor (p75(NTR)). In addition to its expression in the central nervous system, BDNF is found in much greater quantities in blood circulation, where it is largely stored within platelets. Levels 100- to 1,000-fold those of neurons make platelets the most important peripheral reservoir of BDNF. This led us to hypothesize that platelets would express canonical BDNF receptors, i.e., TrkB and p75(NTR), and that the receptors on platelets would bear significant resemblance to the ones found in the brain. However, herein we report discrepancies regarding detection of these receptors using antibody-based assays, with antibodies displaying important tissue-specificity. The currently available antibodies raised against TrkB and p75(NTR) should therefore be used with caution to study platelets as models for neurological disorders. Rigorous characterization of antibodies and bioassays appears critical to understand the interplay between platelet and neuronal biology of BDNF.

Automated summary

Platelets and neurons share many similarities in terms of secretory mechanisms and neurotransmitter regulation, with platelets serving as a potential peripheral biomarker for neuronal pathologies due to their high levels of brain-derived neurotrophic factor (BDNF). Despite the abundance of BDNF in platelets, discrepancies in the detection of BDNF receptors on platelets, such as TrkB and p75(NTR), suggest caution in using antibody-based assays for studying neurological disorders. Rigorous characterization of antibodies and bioassays is crucial to understanding the relationship between platelet and neuronal biology of BDNF.