TY - JOUR
T1 - Plasma metabolites associated with biomarker evidence of neurodegeneration in cognitively normal older adults
AU - Chatterjee, Pratishtha
AU - Cheong, Yeo Jin
AU - Bhatnagar, Atul
AU - Goozee, Kathryn
AU - Wu, Yunqi
AU - McKay, Matthew
AU - Martins, Ian J.
AU - Lim, Wei L.F.
AU - Pedrini, Steve
AU - Tegg, Michelle
AU - Villemagne, Victor L.
AU - Asih, Prita R.
AU - Dave, Preeti
AU - Shah, Tejal M.
AU - Dias, Cintia B.
AU - Fuller, Stephanie J.
AU - Hillebrandt, Heidi
AU - Gupta, Sunil
AU - Hone, Eugene
AU - Taddei, Kevin
AU - Zetterberg, Henrik
AU - Blennow, Kaj
AU - Sohrabi, Hamid R.
AU - Martins, Ralph N.
PY - 2021/10
Y1 - 2021/10
N2 - 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. (Figure presented.).
AB - 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. (Figure presented.).
KW - Alzheimer's disease
KW - biomarkers
KW - metabolomics
KW - neurodegeneration
KW - neurofilament light
KW - preclinical Alzheimer's disease
UR - http://www.scopus.com/inward/record.url?scp=85088793596&partnerID=8YFLogxK
U2 - 10.1111/jnc.15128
DO - 10.1111/jnc.15128
M3 - Article
C2 - 32679614
AN - SCOPUS:85088793596
SN - 0022-3042
VL - 159
SP - 389
EP - 402
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 2
ER -