Plasma metabolites associated with biomarker evidence of neurodegeneration in cognitively normal older adults
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 al...
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| Published in: | Journal of neurochemistry Vol. 159; no. 2; pp. 389 - 402 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
New York
Blackwell Publishing Ltd
01-10-2021
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | 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.
Identifying biochemical changes associated with neurodegeneration prior to symptom onset, will provide insight into the biological mechanisms associated with early neurodegenerative processes, therefore associations between plasma neurofilament light chain (NF‐L), a marker of neurodegeneration, were investigated with plasma metabolites that are products of various cellular processes in cognitively normal older adults. Biogenic amines, amino acids and acylcarnitines correlated positively with plasma NF‐L, suggesting a link between neurodegeneration and biological pathways associated with neurotransmitter regulation, nitric oxide homoeostasis, inflammation and mitochondrial function. Metabolites identified to be associated with plasma NF‐L may have the potential to serve as prognostic markers for neurodegenerative diseases. |
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| Bibliography: | This article is part of the Special Issue “Mass Spectrometry in Alzheimer Disease” ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0022-3042 1471-4159 |
| DOI: | 10.1111/jnc.15128 |