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Metabolic network failures in Alzheimer's disease: A biochemical road map
Toledo JB, Arnold M, Kastenmüller G, Chang R, Baillie RA, Han X, Thambisetty M, Tenenbaum JD et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2017-03-22
Topic: Amyloid, tau and blood-test diagnosis
Introduction The Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, and nonprofit organizations to develop new research directions to transform our understanding of Alzheimer's disease (AD) and propel the development of critically needed therapies. In response to their recommendations, big data at multiple levels are being generated and integrated to study network failures in disease. We used metabolomics as a global biochemical approach to identify peripheral metabolic changes in AD patients and correlate them to cerebrospinal fluid pathology markers, imaging features, and cognitive performance. Methods Fasting serum samples from the Alzheimer's Disease Neuroimaging Initiative (199 control, 356 mild cognitive impairment, and 175 AD participants) were analyzed using the AbsoluteIDQ-p180 kit. Performance was validated in blinded replicates, and values were medication adjusted. Results Multivariable-adjusted analyses showed that sphingomyelins and ether-containing phosphatidylcholines were altered in preclinical biomarker-defined AD stages, whereas acylcarnitines and several amines, including the branched-chain amino acid valine and α-aminoadipic acid, changed in symptomatic stages. Several of the analytes showed consistent associations in the Rotterdam, Erasmus Rucphen Family, and Indiana Memory and Aging Studies. Partial correlation networks constructed for Aβ 1-42 , tau, imaging, and cognitive changes provided initial biochemical insights for disease-related processes. Coexpression networks interconnected key metabolic effectors of disease. Discussion Metabolomics identified key disease-related metabolic changes and disease-progression-related changes. Defining metabolic changes during AD disease trajectory and its relationship to clinical phenotypes provides a powerful roadmap for drug and biomarker discovery.
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APA 7th
Toledo, J. B., Arnold, M., Kastenmüller, G., Chang, R., Baillie, R. A., Han, X., et al. (2017). Metabolic network failures in Alzheimer's disease: A biochemical road map. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1016/j.jalz.2017.01.020
Vancouver
Toledo JB, Arnold M, Kastenmüller G, Chang R, Baillie RA, Han X, et al. Metabolic network failures in Alzheimer's disease: A biochemical road map. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2017. doi:10.1016/j.jalz.2017.01.020. PMID: 28341160.
BibTeX
@article{toledo2017-28341160,
author = {Toledo, J. B. and Arnold, M. and Kastenmüller, G. and Chang, R. and Baillie, R. A. and Han, X. and Thambisetty, M. and Tenenbaum, J. D. and others},
title = {{Metabolic network failures in Alzheimer's disease: A biochemical road map}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2017},
doi = {10.1016/j.jalz.2017.01.020},
pmid = {28341160},
url = {https://doi.org/10.1016/j.jalz.2017.01.020}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Results Multivariable-adjusted analyses showed that sphingomyelins and ether-containing phosphatidylcholines were altered in preclinical biomarker-defined AD stages, whereas acylcarnitines and several amines, including the branched-chain amino acid valine and α-aminoadipic acid, changed in symptomatic stages.
Why it matters
This metabolomics study found that sphingomyelins and ether-containing phosphatidylcholines were altered in preclinical biomarker-defined Alzheimer's stages, while acylcarnitines and several amines changed in symptomatic stages. These findings identify peripheral metabolic changes that may relate to disease stage, but they do not demonstrate any treatment or prevention.
Study details
- Evidence strengthLow
How this study scored 56/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2017 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 474 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 43.1 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 5 / 6 | Cited 28.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 15 other studies in this library |
| Still being cited | 3 / 4 | Cited 128 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Rima F Kaddurah-Daouk: h-index 74 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | National Institutes of Health: institution h-index 2,723 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 22 institution(s) in 6 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28341160) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.jalz.2017.01.020
- PubMed: 28341160
- Original source →
- Free full text: Leiden Repository (Leiden University) →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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