Brain Expression Levels of Commonly Measured Blood Biomarkers of Neurological Damage Differ with Respect to Sex, Race, and Age
Issued Date
2024-07-23
Resource Type
ISSN
03064522
eISSN
18737544
Scopus ID
2-s2.0-85194939451
Pubmed ID
38762083
Journal Title
Neuroscience
Volume
551
Start Page
79
End Page
93
Rights Holder(s)
SCOPUS
Bibliographic Citation
Neuroscience Vol.551 (2024) , 79-93
Suggested Citation
O'Connell G.C., Smothers C.G., Wang J., Ruksakulpiwat S., Armentrout B.L. Brain Expression Levels of Commonly Measured Blood Biomarkers of Neurological Damage Differ with Respect to Sex, Race, and Age. Neuroscience Vol.551 (2024) , 79-93. 93. doi:10.1016/j.neuroscience.2024.05.017 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/98665
Title
Brain Expression Levels of Commonly Measured Blood Biomarkers of Neurological Damage Differ with Respect to Sex, Race, and Age
Author's Affiliation
Corresponding Author(s)
Other Contributor(s)
Abstract
It is increasingly evident that blood biomarkers have potential to improve the diagnosis and management of both acute and chronic neurological conditions. The most well-studied candidates, and arguably those with the broadest utility, are proteins that are highly enriched in neural tissues and released into circulation upon cellular damage. It is currently unknown how the brain expression levels of these proteins is influenced by demographic factors such as sex, race, and age. Given that source tissue abundance is likely a key determinant of the levels observed in the blood during neurological pathology, understanding such influences is important in terms of identifying potential clinical scenarios that could produce diagnostic bias. In this study, we leveraged existing mRNA sequencing data originating from 2,642 normal brain specimens harvested from 382 human donors to examine potential demographic variability in the expression levels of genes which code for 28 candidate blood biomarkers of neurological damage. Existing mass spectrometry data originating from 26 additional normal brain specimens harvested from 26 separate human donors was subsequently used to tentatively assess whether observed transcriptional variance was likely to produce corresponding variance in terms of protein abundance. Genes associated with several well-studied or emerging candidate biomarkers including neurofilament light chain (NfL), ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1), neuron-specific enolase (NSE), and synaptosomal-associated protein 25 (SNAP-25) exhibited significant differences in expression with respect to sex, race, and age. In many instances, these differences in brain expression align well with and provide a mechanistic explanation for previously reported differences in blood levels.