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Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer's disease
Hofmann A, Häsler LM, Lambert M, Kaeser SA, Gräber-Sultan S, Obermüller U, Kuder-Buletta E, la Fougere C et al.. Nature communications, 2024-11-18
Topic: Amyloid, tau and blood-test diagnosis
Disease-modifying therapies for Alzheimer's disease (AD) are likely to be most beneficial when initiated in the presymptomatic phase. To track the benefit of such interventions, fluid biomarkers are of great importance, with neurofilament light chain protein (NfL) showing promise for monitoring neurodegeneration and predicting cognitive outcomes. Here, we update and complement previous findings from the Dominantly Inherited Alzheimer Network Observational Study by using matched cross-sectional and longitudinal cerebrospinal fluid (CSF) and plasma samples from 567 individuals, allowing timely comparative analyses of CSF and blood trajectories across the entire disease spectrum. CSF and plasma trajectories were similar at presymptomatic stages, discriminating mutation carriers from non-carrier controls 10-20 years before the estimated onset of clinical symptoms, depending on the statistical model used. However, after symptom onset the rate of change in CSF NfL continued to increase steadily, whereas the rate of change in plasma NfL leveled off. Both plasma and CSF NfL changes were associated with grey-matter atrophy, but not with Aβ-PET changes, supporting a temporal decoupling of Aβ deposition and neurodegeneration. These observations support NfL in both CSF and blood as an early marker of neurodegeneration but suggest that NfL measured in the CSF may be better suited for monitoring clinical trial outcomes in symptomatic AD patients.
Key findings
- Both plasma and CSF NfL changes were associated with grey-matter atrophy, but not with Aβ-PET changes, supporting a temporal decoupling of Aβ deposition and neurodegeneration.
- These observations support NfL in both CSF and blood as an early marker of neurodegeneration but suggest that NfL measured in the CSF may be better suited for monitoring clinical trial outcomes in symptomatic AD patients.
Why it matters
In autosomal dominant Alzheimer's disease, cerebrospinal fluid and plasma neurofilament light chain trajectories were similar at presymptomatic stages and discriminated mutation carriers from non-carrier controls 10-20 years before estimated symptom onset, but after symptom onset the rate of change in cerebrospinal fluid continued to increase while the rate in plasma leveled off. Both plasma and cerebrospinal fluid changes were associated with grey-matter atrophy but not with Aβ-PET changes, supporting neurofilament light chain in both fluids as an early marker of neurodegeneration, though this concerns monitoring rather than treatment, cure, or prevention.
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Study details
- Study designcross-sectional
- Participants567
- Evidence strengthModerate
How this study scored 63/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature communications) |
| Journal's citation record | 4 / 4 | Nature Communications: journal h-index 747 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 567 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 34 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.5 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 4 / 6 | Cited 8.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 34 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 0 / 4 | Last-listed author Jacqueline Rizzo: h-index 3 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 40 institution(s) in 9 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39557867) |
| Free to read | 2 / 2 | Free to read |
| Total | 63 / 100 | — |
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Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Hofmann, A., Häsler, L. M., Lambert, M., Kaeser, S. A., Gräber-Sultan, S., Obermüller, U., et al. (2024). Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer's disease. Nature communications. https://doi.org/10.1038/s41467-024-52937-8
Vancouver
Hofmann A, Häsler LM, Lambert M, Kaeser SA, Gräber-Sultan S, Obermüller U, et al. Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer's disease. Nature communications. 2024. doi:10.1038/s41467-024-52937-8. PMID: 39557867.
BibTeX
@article{hofmann2024-39557867,
author = {Hofmann, A. and Häsler, L. M. and Lambert, M. and Kaeser, S. A. and Gräber-Sultan, S. and Obermüller, U. and Kuder-Buletta, E. and la Fougere, C. and others},
title = {{Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer's disease}},
journal = {Nature communications},
year = {2024},
doi = {10.1038/s41467-024-52937-8},
pmid = {39557867},
url = {https://doi.org/10.1038/s41467-024-52937-8}
}
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