One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond

Background Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults. Methods Cross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1–42 peptide chain [$ Aβ_{1–42} $] >0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status. Results The diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, $ Aβ_{1–42} $, tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine, glycine, methionine, SAH, SAM, serine, cysteine, and Hcy and reached a diagnostic accuracy of 87.5%. CSF SAH and 5-MTHF were associated with CSF tau and p-tau181. Plasma one-carbon metabolites were able to diagnose subjects with a positive CSF profile of AD pathology in APOE ε4 carriers. Conclusions We observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. These metabolites may be particularly critical in APOE ε4 carriers. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Dayon, Loïc [verfasserIn] Guiraud, Seu Ping Corthésy, John Da Silva, Laeticia Migliavacca, Eugenia Tautvydaitė, Domilė Oikonomidi, Aikaterini Moullet, Barbara Henry, Hugues Métairon, Sylviane Marquis, Julien Descombes, Patrick Collino, Sebastiano Martin, François-Pierre J. Montoliu, Ivan Kussmann, Martin Wojcik, Jérôme Bowman, Gene L. Popp, Julius

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Schlagwörter:	Alzheimer’s disease Cognition CSF Homocysteine Metabolomics One-carbon metabolism -adenosyl-L-homocysteine Tau

Anmerkung:	© The Author(s). 2017

Übergeordnetes Werk:	Enthalten in: Alzheimer's research & therapy - London : BioMed Central, 2009, 9(2017), 1 vom: 17. Juni
Übergeordnetes Werk:	volume:9 ; year:2017 ; number:1 ; day:17 ; month:06

Links:	Volltext

DOI / URN:	10.1186/s13195-017-0270-x

Katalog-ID:	SPR030815878

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520			\|a Background Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults. Methods Cross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1–42 peptide chain [$ Aβ_{1–42} $] >0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status. Results The diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, $ Aβ_{1–42} $, tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine, glycine, methionine, SAH, SAM, serine, cysteine, and Hcy and reached a diagnostic accuracy of 87.5%. CSF SAH and 5-MTHF were associated with CSF tau and p-tau181. Plasma one-carbon metabolites were able to diagnose subjects with a positive CSF profile of AD pathology in APOE ε4 carriers. Conclusions We observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. These metabolites may be particularly critical in APOE ε4 carriers.
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allfields	10.1186/s13195-017-0270-x doi (DE-627)SPR030815878 (SPR)s13195-017-0270-x-e DE-627 ger DE-627 rakwb eng Dayon, Loïc verfasserin (orcid)0000-0002-8499-270X aut One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults. Methods Cross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1–42 peptide chain [$ Aβ_{1–42} $] >0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status. Results The diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, $ Aβ_{1–42} $, tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine, glycine, methionine, SAH, SAM, serine, cysteine, and Hcy and reached a diagnostic accuracy of 87.5%. CSF SAH and 5-MTHF were associated with CSF tau and p-tau181. Plasma one-carbon metabolites were able to diagnose subjects with a positive CSF profile of AD pathology in APOE ε4 carriers. Conclusions We observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. These metabolites may be particularly critical in APOE ε4 carriers. Alzheimer’s disease (dpeaa)DE-He213 Cognition (dpeaa)DE-He213 CSF (dpeaa)DE-He213 Homocysteine (dpeaa)DE-He213 Metabolomics (dpeaa)DE-He213 One-carbon metabolism (dpeaa)DE-He213 -adenosyl-L-homocysteine (dpeaa)DE-He213 Tau (dpeaa)DE-He213 Guiraud, Seu Ping aut Corthésy, John aut Da Silva, Laeticia aut Migliavacca, Eugenia aut Tautvydaitė, Domilė aut Oikonomidi, Aikaterini aut Moullet, Barbara aut Henry, Hugues aut Métairon, Sylviane aut Marquis, Julien aut Descombes, Patrick aut Collino, Sebastiano aut Martin, François-Pierre J. aut Montoliu, Ivan aut Kussmann, Martin aut Wojcik, Jérôme aut Bowman, Gene L. aut Popp, Julius aut Enthalten in Alzheimer's research & therapy London : BioMed Central, 2009 9(2017), 1 vom: 17. Juni (DE-627)605683557 (DE-600)2506521-X 1758-9193 nnns volume:9 year:2017 number:1 day:17 month:06 https://dx.doi.org/10.1186/s13195-017-0270-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2017 1 17 06
spelling	10.1186/s13195-017-0270-x doi (DE-627)SPR030815878 (SPR)s13195-017-0270-x-e DE-627 ger DE-627 rakwb eng Dayon, Loïc verfasserin (orcid)0000-0002-8499-270X aut One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults. Methods Cross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1–42 peptide chain [$ Aβ_{1–42} $] >0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status. Results The diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, $ Aβ_{1–42} $, tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine, glycine, methionine, SAH, SAM, serine, cysteine, and Hcy and reached a diagnostic accuracy of 87.5%. CSF SAH and 5-MTHF were associated with CSF tau and p-tau181. Plasma one-carbon metabolites were able to diagnose subjects with a positive CSF profile of AD pathology in APOE ε4 carriers. Conclusions We observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. These metabolites may be particularly critical in APOE ε4 carriers. Alzheimer’s disease (dpeaa)DE-He213 Cognition (dpeaa)DE-He213 CSF (dpeaa)DE-He213 Homocysteine (dpeaa)DE-He213 Metabolomics (dpeaa)DE-He213 One-carbon metabolism (dpeaa)DE-He213 -adenosyl-L-homocysteine (dpeaa)DE-He213 Tau (dpeaa)DE-He213 Guiraud, Seu Ping aut Corthésy, John aut Da Silva, Laeticia aut Migliavacca, Eugenia aut Tautvydaitė, Domilė aut Oikonomidi, Aikaterini aut Moullet, Barbara aut Henry, Hugues aut Métairon, Sylviane aut Marquis, Julien aut Descombes, Patrick aut Collino, Sebastiano aut Martin, François-Pierre J. aut Montoliu, Ivan aut Kussmann, Martin aut Wojcik, Jérôme aut Bowman, Gene L. aut Popp, Julius aut Enthalten in Alzheimer's research & therapy London : BioMed Central, 2009 9(2017), 1 vom: 17. Juni (DE-627)605683557 (DE-600)2506521-X 1758-9193 nnns volume:9 year:2017 number:1 day:17 month:06 https://dx.doi.org/10.1186/s13195-017-0270-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2017 1 17 06
allfields_unstemmed	10.1186/s13195-017-0270-x doi (DE-627)SPR030815878 (SPR)s13195-017-0270-x-e DE-627 ger DE-627 rakwb eng Dayon, Loïc verfasserin (orcid)0000-0002-8499-270X aut One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults. Methods Cross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1–42 peptide chain [$ Aβ_{1–42} $] >0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status. Results The diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, $ Aβ_{1–42} $, tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine, glycine, methionine, SAH, SAM, serine, cysteine, and Hcy and reached a diagnostic accuracy of 87.5%. CSF SAH and 5-MTHF were associated with CSF tau and p-tau181. Plasma one-carbon metabolites were able to diagnose subjects with a positive CSF profile of AD pathology in APOE ε4 carriers. Conclusions We observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. These metabolites may be particularly critical in APOE ε4 carriers. Alzheimer’s disease (dpeaa)DE-He213 Cognition (dpeaa)DE-He213 CSF (dpeaa)DE-He213 Homocysteine (dpeaa)DE-He213 Metabolomics (dpeaa)DE-He213 One-carbon metabolism (dpeaa)DE-He213 -adenosyl-L-homocysteine (dpeaa)DE-He213 Tau (dpeaa)DE-He213 Guiraud, Seu Ping aut Corthésy, John aut Da Silva, Laeticia aut Migliavacca, Eugenia aut Tautvydaitė, Domilė aut Oikonomidi, Aikaterini aut Moullet, Barbara aut Henry, Hugues aut Métairon, Sylviane aut Marquis, Julien aut Descombes, Patrick aut Collino, Sebastiano aut Martin, François-Pierre J. aut Montoliu, Ivan aut Kussmann, Martin aut Wojcik, Jérôme aut Bowman, Gene L. aut Popp, Julius aut Enthalten in Alzheimer's research & therapy London : BioMed Central, 2009 9(2017), 1 vom: 17. Juni (DE-627)605683557 (DE-600)2506521-X 1758-9193 nnns volume:9 year:2017 number:1 day:17 month:06 https://dx.doi.org/10.1186/s13195-017-0270-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2017 1 17 06
allfieldsGer	10.1186/s13195-017-0270-x doi (DE-627)SPR030815878 (SPR)s13195-017-0270-x-e DE-627 ger DE-627 rakwb eng Dayon, Loïc verfasserin (orcid)0000-0002-8499-270X aut One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults. Methods Cross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1–42 peptide chain [$ Aβ_{1–42} $] >0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status. Results The diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, $ Aβ_{1–42} $, tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine, glycine, methionine, SAH, SAM, serine, cysteine, and Hcy and reached a diagnostic accuracy of 87.5%. CSF SAH and 5-MTHF were associated with CSF tau and p-tau181. Plasma one-carbon metabolites were able to diagnose subjects with a positive CSF profile of AD pathology in APOE ε4 carriers. Conclusions We observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. These metabolites may be particularly critical in APOE ε4 carriers. Alzheimer’s disease (dpeaa)DE-He213 Cognition (dpeaa)DE-He213 CSF (dpeaa)DE-He213 Homocysteine (dpeaa)DE-He213 Metabolomics (dpeaa)DE-He213 One-carbon metabolism (dpeaa)DE-He213 -adenosyl-L-homocysteine (dpeaa)DE-He213 Tau (dpeaa)DE-He213 Guiraud, Seu Ping aut Corthésy, John aut Da Silva, Laeticia aut Migliavacca, Eugenia aut Tautvydaitė, Domilė aut Oikonomidi, Aikaterini aut Moullet, Barbara aut Henry, Hugues aut Métairon, Sylviane aut Marquis, Julien aut Descombes, Patrick aut Collino, Sebastiano aut Martin, François-Pierre J. aut Montoliu, Ivan aut Kussmann, Martin aut Wojcik, Jérôme aut Bowman, Gene L. aut Popp, Julius aut Enthalten in Alzheimer's research & therapy London : BioMed Central, 2009 9(2017), 1 vom: 17. Juni (DE-627)605683557 (DE-600)2506521-X 1758-9193 nnns volume:9 year:2017 number:1 day:17 month:06 https://dx.doi.org/10.1186/s13195-017-0270-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2017 1 17 06
allfieldsSound	10.1186/s13195-017-0270-x doi (DE-627)SPR030815878 (SPR)s13195-017-0270-x-e DE-627 ger DE-627 rakwb eng Dayon, Loïc verfasserin (orcid)0000-0002-8499-270X aut One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults. Methods Cross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1–42 peptide chain [$ Aβ_{1–42} $] >0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status. Results The diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, $ Aβ_{1–42} $, tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine, glycine, methionine, SAH, SAM, serine, cysteine, and Hcy and reached a diagnostic accuracy of 87.5%. CSF SAH and 5-MTHF were associated with CSF tau and p-tau181. Plasma one-carbon metabolites were able to diagnose subjects with a positive CSF profile of AD pathology in APOE ε4 carriers. Conclusions We observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. These metabolites may be particularly critical in APOE ε4 carriers. Alzheimer’s disease (dpeaa)DE-He213 Cognition (dpeaa)DE-He213 CSF (dpeaa)DE-He213 Homocysteine (dpeaa)DE-He213 Metabolomics (dpeaa)DE-He213 One-carbon metabolism (dpeaa)DE-He213 -adenosyl-L-homocysteine (dpeaa)DE-He213 Tau (dpeaa)DE-He213 Guiraud, Seu Ping aut Corthésy, John aut Da Silva, Laeticia aut Migliavacca, Eugenia aut Tautvydaitė, Domilė aut Oikonomidi, Aikaterini aut Moullet, Barbara aut Henry, Hugues aut Métairon, Sylviane aut Marquis, Julien aut Descombes, Patrick aut Collino, Sebastiano aut Martin, François-Pierre J. aut Montoliu, Ivan aut Kussmann, Martin aut Wojcik, Jérôme aut Bowman, Gene L. aut Popp, Julius aut Enthalten in Alzheimer's research & therapy London : BioMed Central, 2009 9(2017), 1 vom: 17. Juni (DE-627)605683557 (DE-600)2506521-X 1758-9193 nnns volume:9 year:2017 number:1 day:17 month:06 https://dx.doi.org/10.1186/s13195-017-0270-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2017 1 17 06
language	English
source	Enthalten in Alzheimer's research & therapy 9(2017), 1 vom: 17. Juni volume:9 year:2017 number:1 day:17 month:06
sourceStr	Enthalten in Alzheimer's research & therapy 9(2017), 1 vom: 17. Juni volume:9 year:2017 number:1 day:17 month:06
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Alzheimer’s disease Cognition CSF Homocysteine Metabolomics One-carbon metabolism -adenosyl-L-homocysteine Tau
isfreeaccess_bool	true
container_title	Alzheimer's research & therapy
authorswithroles_txt_mv	Dayon, Loïc @@aut@@ Guiraud, Seu Ping @@aut@@ Corthésy, John @@aut@@ Da Silva, Laeticia @@aut@@ Migliavacca, Eugenia @@aut@@ Tautvydaitė, Domilė @@aut@@ Oikonomidi, Aikaterini @@aut@@ Moullet, Barbara @@aut@@ Henry, Hugues @@aut@@ Métairon, Sylviane @@aut@@ Marquis, Julien @@aut@@ Descombes, Patrick @@aut@@ Collino, Sebastiano @@aut@@ Martin, François-Pierre J. @@aut@@ Montoliu, Ivan @@aut@@ Kussmann, Martin @@aut@@ Wojcik, Jérôme @@aut@@ Bowman, Gene L. @@aut@@ Popp, Julius @@aut@@
publishDateDaySort_date	2017-06-17T00:00:00Z
hierarchy_top_id	605683557
id	SPR030815878
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR030815878</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519203602.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2017 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s13195-017-0270-x</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR030815878</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s13195-017-0270-x-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Dayon, Loïc</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-8499-270X</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2017</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s). 2017</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults. Methods Cross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1–42 peptide chain [$ Aβ_{1–42} $] >0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status. Results The diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, $ Aβ_{1–42} $, tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine, glycine, methionine, SAH, SAM, serine, cysteine, and Hcy and reached a diagnostic accuracy of 87.5%. CSF SAH and 5-MTHF were associated with CSF tau and p-tau181. Plasma one-carbon metabolites were able to diagnose subjects with a positive CSF profile of AD pathology in APOE ε4 carriers. Conclusions We observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. 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author	Dayon, Loïc
spellingShingle	Dayon, Loïc misc Alzheimer’s disease misc Cognition misc CSF misc Homocysteine misc Metabolomics misc One-carbon metabolism misc -adenosyl-L-homocysteine misc Tau One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond
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topic_title	One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond Alzheimer’s disease (dpeaa)DE-He213 Cognition (dpeaa)DE-He213 CSF (dpeaa)DE-He213 Homocysteine (dpeaa)DE-He213 Metabolomics (dpeaa)DE-He213 One-carbon metabolism (dpeaa)DE-He213 -adenosyl-L-homocysteine (dpeaa)DE-He213 Tau (dpeaa)DE-He213
topic	misc Alzheimer’s disease misc Cognition misc CSF misc Homocysteine misc Metabolomics misc One-carbon metabolism misc -adenosyl-L-homocysteine misc Tau
topic_unstemmed	misc Alzheimer’s disease misc Cognition misc CSF misc Homocysteine misc Metabolomics misc One-carbon metabolism misc -adenosyl-L-homocysteine misc Tau
topic_browse	misc Alzheimer’s disease misc Cognition misc CSF misc Homocysteine misc Metabolomics misc One-carbon metabolism misc -adenosyl-L-homocysteine misc Tau
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title	One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond
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title_full	One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond
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author_browse	Dayon, Loïc Guiraud, Seu Ping Corthésy, John Da Silva, Laeticia Migliavacca, Eugenia Tautvydaitė, Domilė Oikonomidi, Aikaterini Moullet, Barbara Henry, Hugues Métairon, Sylviane Marquis, Julien Descombes, Patrick Collino, Sebastiano Martin, François-Pierre J. Montoliu, Ivan Kussmann, Martin Wojcik, Jérôme Bowman, Gene L. Popp, Julius
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title_sort	one-carbon metabolism, cognitive impairment and csf measures of alzheimer pathology: homocysteine and beyond
title_auth	One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond
abstract	Background Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults. Methods Cross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1–42 peptide chain [$ Aβ_{1–42} $] >0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status. Results The diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, $ Aβ_{1–42} $, tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine, glycine, methionine, SAH, SAM, serine, cysteine, and Hcy and reached a diagnostic accuracy of 87.5%. CSF SAH and 5-MTHF were associated with CSF tau and p-tau181. Plasma one-carbon metabolites were able to diagnose subjects with a positive CSF profile of AD pathology in APOE ε4 carriers. Conclusions We observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. These metabolites may be particularly critical in APOE ε4 carriers. © The Author(s). 2017
abstractGer	Background Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults. Methods Cross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1–42 peptide chain [$ Aβ_{1–42} $] >0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status. Results The diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, $ Aβ_{1–42} $, tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine, glycine, methionine, SAH, SAM, serine, cysteine, and Hcy and reached a diagnostic accuracy of 87.5%. CSF SAH and 5-MTHF were associated with CSF tau and p-tau181. Plasma one-carbon metabolites were able to diagnose subjects with a positive CSF profile of AD pathology in APOE ε4 carriers. Conclusions We observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. These metabolites may be particularly critical in APOE ε4 carriers. © The Author(s). 2017
abstract_unstemmed	Background Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults. Methods Cross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1–42 peptide chain [$ Aβ_{1–42} $] >0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status. Results The diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, $ Aβ_{1–42} $, tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine, glycine, methionine, SAH, SAM, serine, cysteine, and Hcy and reached a diagnostic accuracy of 87.5%. CSF SAH and 5-MTHF were associated with CSF tau and p-tau181. Plasma one-carbon metabolites were able to diagnose subjects with a positive CSF profile of AD pathology in APOE ε4 carriers. Conclusions We observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. These metabolites may be particularly critical in APOE ε4 carriers. © The Author(s). 2017
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title_short	One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond
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up_date	2024-07-03T20:17:03.447Z
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fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR030815878</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519203602.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2017 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s13195-017-0270-x</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR030815878</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s13195-017-0270-x-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Dayon, Loïc</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-8499-270X</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2017</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s). 2017</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults. Methods Cross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1–42 peptide chain [$ Aβ_{1–42} $] >0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status. Results The diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, $ Aβ_{1–42} $, tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine, glycine, methionine, SAH, SAM, serine, cysteine, and Hcy and reached a diagnostic accuracy of 87.5%. CSF SAH and 5-MTHF were associated with CSF tau and p-tau181. Plasma one-carbon metabolites were able to diagnose subjects with a positive CSF profile of AD pathology in APOE ε4 carriers. Conclusions We observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. 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One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond

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