Neurospecific Molecules Measured in Periphery in Humans: How Do They Correlate with the Brain Levels? A Systematic Review

Abstract

Human brain state is usually estimated by brain-specific substances in peripheral tissues, but, for most analytes, a concordance between their content in the brain and periphery is unclear. In this systematic review, we summarized the investigated correlations in humans. PubMed was searched up to June 2022. We included studies measuring the same endogenous neurospecific analytes in the central nervous system and periphery in the same subjects. Not eligible were studies of cerebrospinal fluid, with significant blood–brain barrier disruption, of molecules with well-established blood-periphery concordance or measured in brain tumors. Seventeen studies were eligible. Four studies did not report on correlation and four revealed no significant correlation. Four molecules were examined twice. For BDNF, there was no correlation in both studies. For phenylalanine, glutamine, and glutamate, results were contradictory. Strong correlations were found for free tryptophan (r = 0.97) and translocator protein (r = 0.90). Thus, only for three molecules was there some certainty. BDNF in plasma or serum does not reflect brain content, whereas free tryptophan (in plasma) and translocator protein (in blood cells) can serve as peripheral biomarkers. We expect a breakthrough in the field with advanced in vivo metabolomic analyses, neuroimaging techniques, and blood assays for exosomes of brain origin.

Brain-Derived Neurotrophic Factor (BDNF) as an Indicator for Effects of Cognitive Behavioral Therapy (CBT): A Systematic Review

“…Serum BDNF levels were conducted in each of the included studies. However, the data included in the systematic review conducted by Tikhonova et al [27] suggest that plasma or serum levels do not correlate with brain BDNF levels. More studies including the measures in the central nervous system are needed.…”

Concordance between the In Vivo Content of Neurospecific Proteins (BDNF, NSE, VILIP-1, S100B) in the Hippocampus and Blood in Patients with Epilepsy

“…Thus, in vivo human studies are of particular value, although in vivo determination of analyte content in the human brain is a non-trivial and difficult task due to the limited availability of human brain tissue for research because of ethical standards and technical capabilities. Further progress in the field would be provided by the development of advanced in vivo metabolomic analyses, neuroimaging techniques, and blood assays for exosomes of brain origin, as well as the emergence of novel approaches [ 9 ].…”

“…Hence, the study of neurospecific molecules and the correspondence of their content between the brain and periphery is of great interest. However, quite a few studies have investigated the correlation for neurospecific molecules between the brain and periphery in humans [9]. For example, the study by Gadad et al (2021) revealed a positive correlation between the levels of IL-6 and GDNF in the brain (Brodmann area) and blood plasma [27].…”

“…In humans, there are a few studies comparing BDNF levels in the brain and peripheral tissues. In a systematic review of the literature, we found only three studies, in which no significant correlations between the levels of BDNF in the brain and in human plasma/serum were reported [ 9 ]. However, it should be noted that two of these studies were performed using post mortem material, and the in vivo study had a very small sample size (nine children with epilepsy), and no analysis of the correlations was reported.…”

“…In vivo detection of an analyte content in the human brain is a non-trivial and difficult task due to the limited availability of human brain tissue for research because of ethical standards and technical restrictions. One available approach is to take brain tissue during brain surgery [ 9 ]. This work was performed on biosamples of hippocampal tissue and blood taken in vivo from patients who underwent elective hippocampal resection surgery for drug-resistant epilepsy.…”