Dataset Information

Twin study shows association between monocyte chemoattractant protein-1 and kynurenic acid in cerebrospinal fluid.

ABSTRACT: Preclinical studies indicate a link between the kynurenine pathway and monocyte chemoattractant protein-1 (MCP-1), but there is a lack of clinical studies examining this further. We here perform a secondary analysis of kynurenine metabolites and MCP-1 in cerebrospinal fluid of 23 twins affected from schizophrenia, bipolar disorder or unaffected. We show an association between MCP-1 and kynurenic acid (KYNA), driven by unique environmental influences and a less pronounced association between MCP-1 and tryptophan. No association was detected between MCP-1 and quinolinic acid. Further studies on the mechanism behind the putative relationship between KYNA and MCP-1 are needed.

SUBMITTER: Johansson V

PROVIDER: S-EPMC7474706 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Twin study shows association between monocyte chemoattractant protein-1 and kynurenic acid in cerebrospinal fluid.

Johansson Viktoria V Erhardt Sophie S Engberg Göran G Kegel Magdalena M Bhat Maria M Schwieler Lilly L Blennow Kaj K Zetterberg Henrik H Cannon Tyrone D TD Wetterberg Lennart L Hultman Christina M CM Landén Mikael M

European archives of psychiatry and clinical neuroscience 20190713 7

Preclinical studies indicate a link between the kynurenine pathway and monocyte chemoattractant protein-1 (MCP-1), but there is a lack of clinical studies examining this further. We here perform a secondary analysis of kynurenine metabolites and MCP-1 in cerebrospinal fluid of 23 twins affected from schizophrenia, bipolar disorder or unaffected. We show an association between MCP-1 and kynurenic acid (KYNA), driven by unique environmental influences and a less pronounced association between MCP- ...[more]

PMID: 31302732

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Project description:Alzheimer's disease (AD) pathology is characterized by an early and prolonged decrease in the amyloid peptide (A?) levels concomitant with a later increase in phospho-tau concentrations in cerebrospinal fluid (CSF). We propose that changes in lipid metabolism can contribute to the abnormal processing of A?42 in AD. Our aim was to determine if polyunsaturated fatty acid (PUFA) metabolism can differentiate pre-symptomatic AD from normal aging and symptomatic AD. Using neuropsychology measures and A?42/T-tau in cerebrospinal fluid (CSF), we classify three groups of elderly study participants: cognitively healthy with normal A?42/T-tau (CH-NAT), cognitively healthy with pathological A?42/T-tau (CH-PAT), and AD individuals. We determined the size distribution and the concentration of CSF particles using light scattering and quantified PUFA composition in the nanoparticulate (NP) fraction, supernatant fluid (SF), and unesterified PUFA levels using gas chromatography combined with mass spectrometry. Four PUFAs (C20:2n-6, C20:3n-3, C22:4n-6, C22:5n-3) were enriched in NP of AD compared with CH-NAT. C20:3n-3 levels were higher in the NP fraction from AD compared with CH-PAT. When normalized to the number of NPs in CSF, PUFA levels were significantly higher in CH-NAT and CH-PAT compared with AD. In the SF fractions, only the levels of docosahexaenoic acid (DHA, C22:6n-3) differentiated all three clinical groups. Unesterified DHA was also higher in CH-NAT compared with the other clinical groups. Our studies also show that NP PUFAs in CH participants negatively correlate with CSF A?42 while C20:4n-6, DHA, and n-3 PUFAs in the SF fraction positively correlate with T-tau. The profile of PUFAs in different CSF fractions that correlate with A?42 or with T-tau are different for CH-NAT compared with CH-PAT. These studies show that PUFA metabolism is associated with amyloid and tau processing. Importantly, higher PUFA levels in the cognitively healthy study participants with abnormal A?42/T-tau suggest that PUFA enhances the cognitive resilience of the pre-symptomatic AD population. We propose that interventions that prevent PUFA depletion in the brain may prevent AD pathology by stabilizing A?42 and tau metabolism. Further studies to determine changes in PUFA composition during the progression from pre-symptomatic to AD should reveal novel biomarkers and potential preventive approaches.

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Dataset Information

Twin study shows association between monocyte chemoattractant protein-1 and kynurenic acid in cerebrospinal fluid.

Publications

Twin study shows association between monocyte chemoattractant protein-1 and kynurenic acid in cerebrospinal fluid.

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