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Glial Fibrillary Acidic Protein and Neurofilament Light Reference Intervals in Healthy Individuals
Rebecca Z. Rousset, Madison I. J. Honey, Anouk den Braber, Wiesje M. van der Flier, Henne Holstege, Linda Lorenz, Mark H. J. Wessels, Joep Killestein et al.. JAMA Network Open, 2026-05-14
Topic: Brain proteins, microglia and lab models
In 7989 cognitively unimpaired participants (median [range] age, 54 [30-90] years; 4877 [61.3%] female; mean [SD] BMI, 25.9 [4.2]; mean [SD] eGFR, 80.7 [14.7] mL/min/1.73 m2), older age, lower BMI, and reduced kidney function were associated with increased NfL and GFAP concentrations; female sex was associated with increased GFAP concentrations. Median NfL and GFAP concentrations were 6.58 (6.58-6.58) pg/mL and 23.4 (23.4-23.4) pg/mL higher, respectively, in participants with severe compared with no kidney damage (ie, 45 mL/min/1.73 m2 vs 90 mL/min/1.73 m2). Median NfL and GFAP concentrations were 1.72 (1.72-1.72) pg/mL and 12.6 (12.6-12.6) pg/mL lower, respectively, in participants with obesity compared with those with normal weight (ie, BMI of 30 vs 20). Median GFAP concentrations were 6.17 (6.17-6.17) pg/mL higher in female compared with male participants. NfL concentrations were most elevated in participants with FTD (165 of 179 participants [92.2%] had concentrations greater than the median) and VaD (55 of 60 participants [91.7%] had concentrations greater than the median). GFAP concentrations were most elevated in participants with AD dementia (396 of 479 participants [82.7%] had concentrations greater than the median). A user-friendly interface was developed to visualize the biomarker RIs in the context of an individual's age, BMI, eGFR, and sex. Conclusions and Relevance: In this cross-sectional study of 7958 individuals, RIs to identify normal or abnormal biomarker concentrations in the context of a cognitively unimpaired individuals were established to aid the use of plasma NfL and GFAP measures in clinical practice for neurological diseases.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Rousset, R. Z., Honey, M. I. J., den Braber, A., van der Flier, W. M., Holstege, H., Lorenz, L., et al. (2026). Glial Fibrillary Acidic Protein and Neurofilament Light Reference Intervals in Healthy Individuals. JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2026.12793
Vancouver
Rousset RZ, Honey MIJ, den Braber A, van der Flier WM, Holstege H, Lorenz L, et al. Glial Fibrillary Acidic Protein and Neurofilament Light Reference Intervals in Healthy Individuals. JAMA Network Open. 2026. doi:10.1001/jamanetworkopen.2026.12793. PMID: 42133312.
BibTeX
@article{rousset2026-42133312,
author = {Rousset, Rebecca Z. and Honey, Madison I. J. and den Braber, Anouk and van der Flier, Wiesje M. and Holstege, Henne and Lorenz, Linda and Wessels, Mark H. J. and Killestein, Joep and others},
title = {{Glial Fibrillary Acidic Protein and Neurofilament Light Reference Intervals in Healthy Individuals}},
journal = {JAMA Network Open},
year = {2026},
doi = {10.1001/jamanetworkopen.2026.12793},
pmid = {42133312},
url = {https://doi.org/10.1001/jamanetworkopen.2026.12793}
}
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
- In 7989 cognitively unimpaired participants (median [range] age, 54 [30-90] years; 4877 [61.3%] female; mean [SD] BMI, 25.9 [4.2]; mean [SD] eGFR, 80.7 [14.7] mL/min/1.73 m2), older age, lower BMI, and reduced kidney function were associated with increased NfL and GFAP concentrations; female sex was associated with increased GFAP concentrations.
- Median NfL and GFAP concentrations were 6.58 (6.58-6.58) pg/mL and 23.4 (23.4-23.4) pg/mL higher, respectively, in participants with severe compared with no kidney damage (ie, 45 mL/min/1.73 m2 vs 90 mL/min/1.73 m2).
- Median NfL and GFAP concentrations were 1.72 (1.72-1.72) pg/mL and 12.6 (12.6-12.6) pg/mL lower, respectively, in participants with obesity compared with those with normal weight (ie, BMI of 30 vs 20).
- Median GFAP concentrations were 6.17 (6.17-6.17) pg/mL higher in female compared with male participants.
- NfL concentrations were most elevated in participants with FTD (165 of 179 participants [92.2%] had concentrations greater than the median) and VaD (55 of 60 participants [91.7%] had concentrations greater than the median).
Why it matters
This study established reference intervals for GFAP and NfL in healthy individuals, showing that age, BMI, kidney function and sex affect these levels. It is about interpreting biomarker measurements, not about treating or preventing Alzheimer's disease.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designcross-sectional
- Participants179
- Effect size61.3%; 92.2%; 91.7%
- Evidence strengthLow
How this study scored 55/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 53 of the 96 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA Network Open) |
| Journal's citation record | 2 / 4 | JAMA Network Open: journal h-index 235 (OpenAlex, 2026-10-29) |
| 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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 179 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 4 / 6 | Cited 12.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 1 / 3 | Vrije Universiteit Amsterdam: institution h-index 1,014 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42133312) |
| Free to read | 2 / 2 | Free to read |
| Points | 53 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 53 of the 96 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamanetworkopen.2026.12793
- PubMed: 42133312
- Original source →
- Free full text: JAMA Network Open →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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