Brain Expression Levels of Commonly Measured Blood Biomarkers of Neurological Damage Differ with Respect to Sex, Race, and Age

•Brain expression levels of 28 candidate blood biomarkers of neuropathology were assessed.•Numerous differences were observed with respect to sex, race, and age.•These differences could affect blood levels clinically observed in pathology. It is increasingly evident that blood biomarkers have potent...

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Veröffentlicht in:Neuroscience 2024-07, Vol.551, p.79-93
Hauptverfasser: O'Connell, Grant C., Smothers, Christine G., Wang, Jing, Ruksakulpiwat, Suebsarn, Armentrout, Bethany L.
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Sprache:eng
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Zusammenfassung:•Brain expression levels of 28 candidate blood biomarkers of neuropathology were assessed.•Numerous differences were observed with respect to sex, race, and age.•These differences could affect blood levels clinically observed in pathology. 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.
ISSN:0306-4522
1873-7544
1873-7544
DOI:10.1016/j.neuroscience.2024.05.017