Plasma metabolites associated with biomarker evidence of neurodegeneration in cognitively normal older adults

Pratishtha Chatterjee, Yeo-Jin Cheong, Atul Bhatnagar, Kathryn Goozee, Yunqi Wu, Matthew McKay, Ian J. Martins, Wei Ling Florence Lim, Steve Pedrini, Michelle Tegg, Victor Villemagne, Prita R. Asih, Preeti Dave, Tejal M. Shah, Cintia B. Dias, Stephanie J. Fuller, Heidi Hillebrandt, Sunil Gupta, Eugene Hone, Kevin Taddei & 4 others Henrik Zetterberg, Kaj Blennow, Hamid R. Sohrabi, Ralph N. Martins

Research output: Contribution to journalArticle

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently has no cure. Identifying biochemical changes associated with neurodegeneration prior to symptom onset, will provide insight into the biological mechanisms associated with neurodegenerative processes, that may also aid in identifying potential drug targets. The current study therefore investigated associations between plasma neurofilament light chain (NF-L), a marker of neurodegeneration, with plasma metabolites that are products of various cellular processes. Plasma NF-L, measured by ultrasensitive Single molecule array (Simoa) technology (Quanterix) and plasma metabolites, measured by mass-spectrometry (AbsoluteIDQ® p400HR kit, BIOCRATES), were assessed in the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohort comprising 100 cognitively normal older adults. Metabolites belonging to biogenic amine (creatinine, symmetric dimethylarginine, asymmetric dimethylarginine; ADMA, kynurenine, trans-4-hydroxyproline), amino acid (citrulline, proline, arginine, asparagine, phenylalanine, threonine) and acylcarnitine classes were observed to have positive correlations with plasma NF-L, suggesting a link between neurodegeneration and biological pathways associated with neurotransmitter regulation, nitric oxide homoeostasis, inflammation and mitochondrial function. Additionally, after stratifying participants based on low/high brain amyloid-β load (Aβ ±) assessed by positron emission tomography, while creatinine, SDMA and citrulline correlated with NF-L in both Aβ- and Aβ+ groups, ADMA, proline, arginine, asparagine, phenylalanine and acylcarnitine species correlated with NF-L only in the Aβ+ group after adjusting for confounding variables, suggesting that the association of these metabolites with neurodegeneration may be relevant to AD-related neuropathology. Metabolites identified to be associated with plasma NF-L may have the potential to serve as prognostic markers for neurodegenerative diseases, however, further studies are required to validate the current findings in an independent cohort, both cross-sectionally and longitudinally.

Original languageEnglish
Number of pages15
JournalJournal of Neurochemistry
Early online date17 Jul 2020
DOIs
Publication statusE-pub ahead of print - 17 Jul 2020

Keywords

  • Alzheimer's disease
  • biomarkers
  • metabolomics
  • neurodegeneration
  • neurofilament light
  • preclinical Alzheimer's disease

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