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

Overview of attention for article published in Alzheimer's Research & Therapy, June 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (82nd percentile)

Mentioned by

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1 news outlet
twitter
1 tweeter

Citations

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28 Dimensions

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88 Mendeley
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Title
One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond
Published in
Alzheimer's Research & Therapy, June 2017
DOI 10.1186/s13195-017-0270-x
Pubmed ID
Authors

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

Abstract

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. 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. 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. 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.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 88 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Canada 1 1%
Unknown 87 99%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 15%
Student > Bachelor 12 14%
Student > Ph. D. Student 11 13%
Student > Master 11 13%
Other 4 5%
Other 16 18%
Unknown 21 24%
Readers by discipline Count As %
Medicine and Dentistry 16 18%
Biochemistry, Genetics and Molecular Biology 12 14%
Neuroscience 11 13%
Pharmacology, Toxicology and Pharmaceutical Science 4 5%
Agricultural and Biological Sciences 3 3%
Other 15 17%
Unknown 27 31%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 June 2017.
All research outputs
#1,197,410
of 11,405,459 outputs
Outputs from Alzheimer's Research & Therapy
#190
of 452 outputs
Outputs of similar age
#46,946
of 264,878 outputs
Outputs of similar age from Alzheimer's Research & Therapy
#9
of 14 outputs
Altmetric has tracked 11,405,459 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 452 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 16.4. This one has gotten more attention than average, scoring higher than 55% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 264,878 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 82% of its contemporaries.
We're also able to compare this research output to 14 others from the same source and published within six weeks on either side of this one. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.