Home › Research › Biomarkers
Interplay between Alzheimer and vascular pathology as determinants of plasma neurofilament light in a memory clinic population
Michelle Barboure, Inge M.W. Verberk, Sinthujah Vigneswaran, Frederik Barkhof, Elsmarieke van de Giessen, Geert-Jan Biessels, Charlotte E. Teunissen, Wiesje M. van der Flier et al.. Cerebral Circulation - Cognition and Behavior, 2025-01-01
Topic: Amyloid, tau and blood-test diagnosis
Introduction Plasma neurofilament light (NfL) is increasingly used as a general marker for neurodegeneration in memory clinics to aid differential diagnosis. However, interpreting its levels in the presence of vascular pathology remains unclear. We investigated the individual and combined effects of Alzheimer’s and vascular pathologies on plasma NfL in individuals across the cognitive spectrum. Methods Cross-sectional data from 1221 individuals in the Amsterdam Dementia Cohort were analyzed, including participants with a clinical diagnosis of subjective cognitive decline (SCD, n=421), mild cognitive impairment (MCI, n=369), Alzheimer's disease (AD, n=379), and vascular dementia (VaD, n=52). NfL was measured using SIMOA (Quanterix) and log-transformed. Amyloid pathology was defined by positive CSF/PET biomarkers. Vascular pathology was defined as having a small vessel disease (SVD) score ≥1 (range 0-3), with one point given for each feature present: white matter hyperintensities (Fazekas score ≥2), microbleeds (≥1), and/or lacunes (≥1). Participants were classified by vascular (V) and amyloid (A) status: A-V- (n=293), A-V+ (n=173), A+V- (n=325), A+V+ (n=308). Group differences were assessed using a robust linear model adjusted for age and sex. Multivariate regression examined the effects of amyloid and vascular pathology on NfL, adjusting for age, sex, and syndrome diagnosis (SCD, MCI, dementia). Mediation analysis tested whether effects were mediated via medial temporal lobe (MTA) atrophy. Results NfL levels increased stepwise when comparing A-V- across all other groups, suggesting an additive effect of amyloid and vascular pathologies (Fig 1). Subsequent regression analysis showed that, across the entire group, amyloid and SVD score independently associate with higher NfL levels. An interaction term showed that the impact of SVD score on NfL was moderated by amyloid status, with a stronger association in A- individuals. These patterns persisted in the symptomatic stage (MCI, dementia), whereas in the pre-symptomatic stage (SCD), only amyloid was associated with higher NfL. Their association was not mediated by MTA. Conclusions Vascular burden influences NfL levels, particularly in A- individuals at a symptomatic stage. These results underscore the importance of considering multiple pathologies when interpreting NfL as a neurodegeneration biomarker in memory clinic settings.
Key findings
- Results NfL levels increased stepwise when comparing A-V- across all other groups, suggesting an additive effect of amyloid and vascular pathologies (Fig 1).
- Subsequent regression analysis showed that, across the entire group, amyloid and SVD score independently associate with higher NfL levels.
- An interaction term showed that the impact of SVD score on NfL was moderated by amyloid status, with a stronger association in A- individuals.
- These patterns persisted in the symptomatic stage (MCI, dementia), whereas in the pre-symptomatic stage (SCD), only amyloid was associated with higher NfL.
- These results underscore the importance of considering multiple pathologies when interpreting NfL as a neurodegeneration biomarker in memory clinic settings.
Why it matters
In 1221 memory clinic participants, plasma neurofilament light rose stepwise with combined amyloid and vascular pathology, and both amyloid and small vessel disease score were independently linked to higher levels. The authors note the effect of small vessel disease on neurofilament light was stronger in people without amyloid pathology.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designcross-sectional
- Participants421
- Evidence strengthModerate
How this study scored 41/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and 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 39 of the 96 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cerebral Circulation - Cognition and Behavior) |
| Journal's citation record | 0 / 4 | Cerebral Circulation - Cognition and Behavior: journal h-index 19 (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 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 421 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 | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 0 / 6 | Cited 0.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 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 | University Medical Center Utrecht: institution h-index 1,076 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 39 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 39 of the 96 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.cccb.2025.100471
- Original source →
- Free full text: Cerebral Circulation - Cognition and Behavior →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Barboure, M., Verberk, I. M., Vigneswaran, S., Barkhof, F., van de Giessen, E., Biessels, G.-J., et al. (2025). Interplay between Alzheimer and vascular pathology as determinants of plasma neurofilament light in a memory clinic population. Cerebral Circulation - Cognition and Behavior. https://doi.org/10.1016/j.cccb.2025.100471
Vancouver
Barboure M, Verberk IM, Vigneswaran S, Barkhof F, van de Giessen E, Biessels G.-J, et al. Interplay between Alzheimer and vascular pathology as determinants of plasma neurofilament light in a memory clinic population. Cerebral Circulation - Cognition and Behavior. 2025. doi:10.1016/j.cccb.2025.100471.
BibTeX
@article{barboure2025-a8b97e3a,
author = {Barboure, Michelle and Verberk, Inge M.W. and Vigneswaran, Sinthujah and Barkhof, Frederik and van de Giessen, Elsmarieke and Biessels, Geert-Jan and Teunissen, Charlotte E. and van der Flier, Wiesje M. and others},
title = {{Interplay between Alzheimer and vascular pathology as determinants of plasma neurofilament light in a memory clinic population}},
journal = {Cerebral Circulation - Cognition and Behavior},
year = {2025},
doi = {10.1016/j.cccb.2025.100471},
url = {https://doi.org/10.1016/j.cccb.2025.100471}
}
Related studies in Biomarkers
Also tagged “biomarkers”
821 studies in the library carry the topic tag “biomarkers”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 821 tagged studies.