One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond
| Autor: | Jérôme Wojcik, Martin Kussmann, Gene L. Bowman, Laeticia Da Silva, John Corthésy, François-Pierre Martin, Loïc Dayon, Ivan Montoliu, Hugues Henry, Barbara Moullet, Sylviane Metairon, Seu Ping Guiraud, Eugenia Migliavacca, Julien Marquis, Julius Popp, Patrick Descombes, Domilė Tautvydaitė, Sebastiano Collino, Aikaterini Oikonomidi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Male Pathology Biomarkers/blood/cerebrospinal fluid Homocysteine Carbon Compounds Inorganic Comorbidity lcsh:RC346-429 chemistry.chemical_compound ddc:616.89 Cognition 0302 clinical medicine Cerebrospinal fluid Switzerland/epidemiology Risk Factors Prevalence Cognitive decline Carbon Compounds Inorganic/cerebrospinal fluid biology S-adenosyl-L-homocysteine One-carbon metabolism Neurology Homocysteine/cerebrospinal fluid Cognition Disorders/cerebrospinal fluid/diagnosis/epidemiology Female Alzheimer's disease Carbon/blood Psychology Alzheimer’s disease Switzerland medicine.medical_specialty Hyperhomocysteinemia Cognitive Neuroscience CSF lcsh:RC321-571 03 medical and health sciences Alzheimer Disease medicine Metabolomics Humans Aged Alzheimer Disease/cerebrospinal fluid Alzheimer Disease/diagnosis Alzheimer Disease/epidemiology Biomarkers/blood Biomarkers/cerebrospinal fluid Cognition Disorders/cerebrospinal fluid Cognition Disorders/diagnosis Cognition Disorders/epidemiology Tau lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry lcsh:Neurology. Diseases of the nervous system Methionine Research medicine.disease Cystathionine beta synthase Carbon Alzheimer Disease/cerebrospinal fluid/diagnosis/epidemiology 030104 developmental biology chemistry biology.protein Neurology (clinical) Cognition Disorders Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | Alzheimer's Research and Therapy, Vol. 9, No 1 (2017) P. 43 Alzheimer’s Research & Therapy, Vol 9, Iss 1, Pp 1-11 (2017) Alzheimer's research & therapy, vol. 9, no. 1, pp. 43 Alzheimer's Research & Therapy |
| ISSN: | 1758-9193 |
| Popis: | 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 [Aβ1–42] >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, Aβ1–42, 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. Electronic supplementary material The online version of this article (doi:10.1186/s13195-017-0270-x) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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