Document Type
Journal Article
Publication Title
Journal of Neuroinflammation
ISSN
1742-2094
Volume
16
PubMed ID
31601232
Publisher
Springer
School
School of Medical and Health Sciences
RAS ID
30150
Funders
This study was funded by the Anglicare, Sydney; the Australian Alzheimer’s Research Foundation (AARF), Perth; and the KaRa Institute of Neurological Diseases (KaRa MINDS), Sydney. HZ is a Wallenberg Academy Fellow supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), and the Swedish State Support for Clinical Research (#ALFGBG-720931). KG is a recipient of the Cooperative Research Centre for Mental Health top-up scholarship.
Abstract
BACKGROUND: Blood markers indicative of neurodegeneration (neurofilament light chain; NFL), Alzheimer's disease amyloid pathology (amyloid-β; Aβ), and neuroinflammation (kynurenine pathway; KP metabolites) have been investigated independently in neurodegenerative diseases. However, the association of these markers of neurodegeneration and AD pathology with neuroinflammation has not been investigated previously. Therefore, the current study examined whether NFL and Aβ correlate with KP metabolites in elderly individuals to provide insight on the association between blood indicators of neurodegeneration and neuroinflammation.
METHODS: Correlations between KP metabolites, measured using liquid chromatography and gas chromatography coupled with mass spectrometry, and plasma NFL and Aβ concentrations, measured using single molecule array (Simoa) assays, were investigated in elderly individuals aged 65-90 years, with normal global cognition (Mini-Mental State Examination Score ≥ 26) from the Kerr Anglican Retirement Village Initiative in Ageing Health cohort.
RESULTS: A positive correlation between NFL and the kynurenine to tryptophan ratio (K/T) reflecting indoleamine 2,3-dioxygenase activity was observed (r = .451, p < .0001). Positive correlations were also observed between NFL and kynurenine (r = .364, p < .0005), kynurenic acid (r = .384, p < .0001), 3-hydroxykynurenine (r = .246, p = .014), anthranilic acid (r = .311, p = .002), and quinolinic acid (r = .296, p = .003). Further, significant associations were observed between plasma Aβ40 and the K/T (r = .375, p < .0005), kynurenine (r = .374, p < .0005), kynurenic acid (r = .352, p < .0005), anthranilic acid (r = .381, p < .0005), and quinolinic acid (r = .352, p < .0005). Significant associations were also observed between plasma Aβ42 and the K/T ratio (r = .215, p = .034), kynurenic acid (r = .214, p = .035), anthranilic acid (r = .278, p = .006), and quinolinic acid (r = .224, p = .027) in the cohort. On stratifying participants based on their neocortical Aβ load (NAL) status, NFL correlated with KP metabolites irrespective of NAL status; however, associations between plasma Aβ and KP metabolites were only pronounced in individuals with high NAL while associations in individuals with low NAL were nearly absent.
CONCLUSIONS: The current study shows that KP metabolite changes are associated with biomarker evidence of neurodegeneration. Additionally, the association between KP metabolites and plasma Aβ seems to be NAL status dependent. Finally, the current study suggests that an association between neurodegeneration and neuroinflammation manifests in the periphery, suggesting that preventing cytoskeleton cytotoxicity by KP metabolites may have therapeutic potential.
DOI
10.1186/s12974-019-1567-4
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Chatterjee, P., Zetterberg, H., Goozee, K., Lim, C. K., Jacobs, K. R., Ashton, N. J., ... & Martins, R. N. (2019). Plasma neurofilament light chain and amyloid-β are associated with the kynurenine pathway metabolites in preclinical Alzheimer’s disease. Journal of Neuroinflammation, 16.
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