Plasma neurofilament light chain and amyloid-β are associated with the kynurenine pathway metabolites in preclinical Alzheimer’s disease

P. Chatterjee; H. Zetterberg; K. Goozee; C.K. Lim; K.R. Jacobs; N.J. Ashton; A. Hye; S. Pedrini; H.R. Sohrabi; T. Shah; P.R. Asih; P. Dave; K. Shen; K. Taddei; D.B. Lovejoy; G.J. Guillemin; K. Blennow; R.N. Martins

doi:10.1186/s12974-019-1567-4

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Plasma neurofilament light chain and amyloid-β are associated with the kynurenine pathway metabolites in preclinical Alzheimer’s disease

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Plasma neurofilament light chain and amyloid-β are associated with the kynurenine pathway metabolites in preclinical Alzheimer’s disease

P. Chatterjee, H. Zetterberg, K. Goozee, C.K. Lim, K.R. Jacobs, N.J. Ashton, A. Hye, S. Pedrini, H.R. Sohrabi, T. Shah, …

Journal of Neuroinflammation, Vol.16(1), Article number: 186

2019

DOI: https://doi.org/10.1186/s12974-019-1567-4

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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.

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Title: Plasma neurofilament light chain and amyloid-β are associated with the kynurenine pathway metabolites in preclinical Alzheimer’s disease
Authors/Creators: P. Chatterjee (Author/Creator) - Macquarie University
H. Zetterberg (Author/Creator) - University of Gothenburg
K. Goozee (Author/Creator) - Macquarie University
C.K. Lim (Author/Creator) - Macquarie University
K.R. Jacobs (Author/Creator) - Macquarie University
N.J. Ashton (Author/Creator) - University of Gothenburg
A. Hye (Author/Creator) - King's College London
S. Pedrini (Author/Creator) - Edith Cowan University
H.R. Sohrabi (Author/Creator) - Macquarie University
T. Shah (Author/Creator) - Macquarie University
P.R. Asih (Author/Creator) - Macquarie University
P. Dave (Author/Creator) - Macquarie University
K. Shen (Author/Creator) - Australian eHealth Research Centre, CSIRO, Floreat, WA, Australia.
K. Taddei (Author/Creator) - Edith Cowan University
D.B. Lovejoy (Author/Creator) - Macquarie University
G.J. Guillemin (Author/Creator) - Macquarie University
K. Blennow (Author/Creator) - Sahlgrenska University Hospital
R.N. Martins (Author/Creator) - Macquarie University
Publication Details: Journal of Neuroinflammation, Vol.16(1), Article number: 186
Publisher: BMC
Identifiers: 991005542902407891
Copyright: © The Author(s). 2019
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.231 Vitamin Metabolism; 1.231.1938 Tryptophan Metabolism
Web Of Science research areas: Immunology; Neurosciences
ESI research areas: Neuroscience & Behavior