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Sphingolipid metabolism correlates with cerebrospinal fluid Beta amyloid levels in Alzheimer's disease
Alfred N Fonteh, Cora Ormseth, Jiarong Chiang, Matthew Cipolla, Xianghong Arakaki, Michael G Harrington. PloS one, 2015-05-04
Topic: Plasma and spinal-fluid biomarkers
Sphingolipids are important in many brain functions but their role in Alzheimer's disease (AD) is not completely defined. A major limit is availability of fresh brain tissue with defined AD pathology. The discovery that cerebrospinal fluid (CSF) contains abundant nanoparticles that include synaptic vesicles and large dense core vesicles offer an accessible sample to study these organelles, while the supernatant fluid allows study of brain interstitial metabolism. Our objective was to characterize sphingolipids in nanoparticles representative of membrane vesicle metabolism, and in supernatant fluid representative of interstitial metabolism from study participants with varying levels of cognitive dysfunction. We recently described the recruitment, diagnosis, and CSF collection from cognitively normal or impaired study participants. Using liquid chromatography tandem mass spectrometry, we report that cognitively normal participants had measureable levels of sphingomyelin, ceramide, and dihydroceramide species, but that their distribution differed between nanoparticles and supernatant fluid, and further differed in those with cognitive impairment. In CSF from AD compared with cognitively normal participants: a) total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b) levels of ceramide species were lower in nanoparticles and higher in supernatant fluid; c) three sphingomyelin species were reduced in the nanoparticle fraction. Moreover, three sphingomyelin species in the nanoparticle fraction were lower in mild cognitive impairment compared with cognitively normal participants. The activity of acid, but not neutral sphingomyelinase was significantly reduced in the CSF from AD participants. The reduction in acid sphingomylinase in CSF from AD participants was independent of depression and psychotropic medications. Acid sphingomyelinase activity positively correlated with amyloid β42 concentration in CSF from cognitively normal but not impaired participants. In dementia, altered sphingolipid metabolism, decreased acid sphingomyelinase activity and its lost association with CSF amyloid β42 concentration, underscores the potential of sphingolipids as disease biomarkers, and acid sphingomyelinase as a target for AD diagnosis and/or treatment.
Key findings
- In CSF from AD compared with cognitively normal participants: a) total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b) levels of ceramide species were lower in nanoparticles and higher in supernatant fluid; c) three sphingomyelin species were reduced in the nanoparticle fraction.
- Moreover, three sphingomyelin species in the nanoparticle fraction were lower in mild cognitive impairment compared with cognitively normal participants.
- The activity of acid, but not neutral sphingomyelinase was significantly reduced in the CSF from AD participants.
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Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 21 of the 56 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (PloS one) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 1 / 5 | 2015 — within 20 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25938590) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 21 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 21 of the 56 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
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APA 7th
Fonteh, A. N., Ormseth, C., Chiang, J., Cipolla, M., Arakaki, X., & Harrington, M. G. (2015). Sphingolipid metabolism correlates with cerebrospinal fluid Beta amyloid levels in Alzheimer's disease. PloS one. https://doi.org/10.1371/journal.pone.0125597
Vancouver
Fonteh AN, Ormseth C, Chiang J, Cipolla M, Arakaki X, Harrington MG. Sphingolipid metabolism correlates with cerebrospinal fluid Beta amyloid levels in Alzheimer's disease. PloS one. 2015. doi:10.1371/journal.pone.0125597. PMID: 25938590.
BibTeX
@article{fonteh2015-25938590,
author = {Fonteh, Alfred N and Ormseth, Cora and Chiang, Jiarong and Cipolla, Matthew and Arakaki, Xianghong and Harrington, Michael G},
title = {{Sphingolipid metabolism correlates with cerebrospinal fluid Beta amyloid levels in Alzheimer's disease}},
journal = {PloS one},
year = {2015},
doi = {10.1371/journal.pone.0125597},
pmid = {25938590},
url = {https://doi.org/10.1371/journal.pone.0125597}
}