Home › Research › Biomarkers
Levels of Soluble Interleukin 6 Receptor and Asp358Ala Are Associated With Cognitive Performance and Alzheimer Disease Biomarkers
Quillen D, Hughes TM, Craft S, Howard T, Register T, Suerken C, Hawkins GA, Milligan C.. Neurology(R) neuroimmunology & neuroinflammation, 2023-02-21
Topic: Amyloid, tau and blood-test diagnosis
Background and objectives Alzheimer disease (AD) is a neurodegenerative disease process manifesting clinically with cognitive impairment and dementia. AD pathology is complex, and in addition to plaques and tangles, neuroinflammation is a consistent feature. Interleukin (IL) 6 is a multifaceted cytokine involved in a plethora of cellular mechanisms including both anti-inflammatory and inflammatory processes. IL6 can signal classically through the membrane-bound receptor or by IL6 trans-signaling forming a complex with the soluble IL6 receptor (sIL6R) and activating membrane-bound glycoprotein 130 on cells not expressing IL6R. IL6 trans-signaling has been demonstrated as the primary mechanism of IL6-mediated events in neurodegenerative processes. In this study, we performed a cross-sectional analysis to investigate whether inheritance of a genetic variation in the IL6R gene and associated elevated sIL6R levels in plasma and CSF were associated with cognitive performance. Methods We genotyped the IL6R rs2228145 nonsynonymous variant (Asp 358 Ala) and assayed IL6 and sIL6R concentrations in paired samples of plasma and CSF obtained from 120 participants with normal cognition, mild cognitive impairment, or probable AD enrolled in the Wake Forest Alzheimer's Disease Research Center's Clinical Core. IL6 rs2228145 genotype and measures of plasma IL6 and sIL6R were assessed for relationships with cognitive status and clinical data, including the Montreal Cognitive Assessment (MoCA), modified Preclinical Alzheimer's Cognitive Composite (mPACC), cognitive domain scores obtained from the Uniform Data Set, and CSF concentrations of phosphoTau T181 (pTau181), β-amyloid (Aβ) Aβ40 and Aβ42 concentrations. Results We found that inheritance of the IL6R Ala 358 variant and elevated sIL6R levels in plasma and CSF were correlated with lower mPACC, MoCA and memory domain scores, increases in CSF pTau181, and decreases in the CSF Aβ42/40 ratio in both unadjusted and covariate-adjusted statistical models. Discussion These data suggest that IL6 trans-signaling and the inheritance of the IL6R Ala 358 variant are related to reduced cognition and greater levels of biomarkers for AD disease pathology. Follow-up prospective studies are necessary, as patients who inherit IL6R Ala 358 may be identified as ideally responsive to IL6 receptor-blocking therapies.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Quillen, D., Hughes, T. M., Craft, S., Howard, T., Register, T., Suerken, C., et al. (2023). Levels of Soluble Interleukin 6 Receptor and Asp358Ala Are Associated With Cognitive Performance and Alzheimer Disease Biomarkers. Neurology(R) neuroimmunology & neuroinflammation. https://doi.org/10.1212/nxi.0000000000200095
Vancouver
Quillen D, Hughes TM, Craft S, Howard T, Register T, Suerken C, et al. Levels of Soluble Interleukin 6 Receptor and Asp358Ala Are Associated With Cognitive Performance and Alzheimer Disease Biomarkers. Neurology(R) neuroimmunology & neuroinflammation. 2023. doi:10.1212/nxi.0000000000200095. PMID: 36810164.
BibTeX
@article{quillen2023-36810164,
author = {Quillen, D. and Hughes, T. M. and Craft, S. and Howard, T. and Register, T. and Suerken, C. and Hawkins, G. A. and Milligan, C.},
title = {{Levels of Soluble Interleukin 6 Receptor and Asp358Ala Are Associated With Cognitive Performance and Alzheimer Disease Biomarkers}},
journal = {Neurology(R) neuroimmunology \& neuroinflammation},
year = {2023},
doi = {10.1212/nxi.0000000000200095},
pmid = {36810164},
url = {https://doi.org/10.1212/nxi.0000000000200095}
}
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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- IL6 trans-signaling has been demonstrated as the primary mechanism of IL6-mediated events in neurodegenerative processes.
- In this study, we performed a cross-sectional analysis to investigate whether inheritance of a genetic variation in the IL6R gene and associated elevated sIL6R levels in plasma and CSF were associated with cognitive performance.
- Results We found that inheritance of the IL6R Ala 358 variant and elevated sIL6R levels in plasma and CSF were correlated with lower mPACC, MoCA and memory domain scores, increases in CSF pTau181, and decreases in the CSF Aβ42/40 ratio in both unadjusted and covariate-adjusted statistical models.
- Discussion These data suggest that IL6 trans-signaling and the inheritance of the IL6R Ala 358 variant are related to reduced cognition and greater levels of biomarkers for AD disease pathology.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designcross-sectional
- Participants120
- Evidence strengthLow
How this study scored 59/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomized / 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 and multicenter collaboration, so those were left out: it earned 34 of the 58 points we could judge it on, which is 59 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurology(R) neuroimmunology & neuroinflammation) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 120 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36810164) |
| Free to read | 2 / 2 | Free to read |
| Points | 34 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 34 of the 58 points we could judge it on is 59 out of 100. |
| Total | 59 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related
Studies in the library that share something with this one. The line above each title says what.
Related studies in Biomarkers
Also tagged “cognitive-performance”
3 studies in the library carry the topic tag “cognitive-performance”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 3 tagged studies.