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Interplay between Alzheimer and vascular pathology as determinants of plasma neurofilament light in a memory clinic population
Michelle C. Barboure, Inge M.W. Verberk, Sinthujah Vigneswaran, Frederik Barkhof, Elsmarieke van de Giessen, Geert Jan Biessels, Charlotte Elisabeth Teunissen, Wiesje M. van der Flier et al.. Alzheimer s & Dementia, 2025-12-01
Topic: Amyloid, tau and blood-test diagnosis
Abstract Background 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. Method Cross‐sectional data from 1099 individuals in the Amsterdam Dementia Cohort were analyzed, including participants with a clinical diagnosis of subjective cognitive decline (SCD, n = 371), mild cognitive impairment (MCI, n = 326), Alzheimer's disease (AD, n = 347), and vascular dementia (VaD, n = 55). 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 calculated using Kruskal‐Wallis with Bonferroni correction. Multivariate regression analyses investigated the effects of amyloid and vascular pathology on NfL levels, adjusting for age, sex, and syndrome diagnosis. Result NfL levels increased stepwise from A‐V‐ to A+V+ groups, suggesting an additive effect of amyloid and vascular pathologies (Figure 1). Subsequent regression analysis revealed SVD score as a significant predictor of NfL levels, while amyloid status was not (Model 1 and 2, Table 1). An interaction term revealed that amyloid status moderated the effect of SVD score on NfL levels (Model 3). Stratified analysis showed higher baseline NfL levels in amyloid‐positive individuals, with SVD score remaining a significant predictor in both groups. While included as a covariate, dementia diagnosis emerged as a strong determinant of NfL levels, particularly in amyloid‐negative individuals (Figure 2). SVD score explained more variance in amyloid‐negative (40%) than amyloid‐positive (21%) individuals. Conclusion Vascular burden influences NfL levels, particularly in amyloid‐negative individuals. These results underscore the importance of considering multiple pathologies when interpreting NfL as a neurodegeneration biomarker in memory clinic settings.
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APA 7th
Barboure, M. C., 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. Alzheimer s & Dementia. https://doi.org/10.1002/alz70856_104832
Vancouver
Barboure MC, Verberk IM, Vigneswaran S, Barkhof F, van de Giessen E, Biessels GJ, et al. Interplay between Alzheimer and vascular pathology as determinants of plasma neurofilament light in a memory clinic population. Alzheimer s & Dementia. 2025. doi:10.1002/alz70856_104832.
BibTeX
@article{barboure2025-b9e7be23,
author = {Barboure, Michelle C. and Verberk, Inge M.W. and Vigneswaran, Sinthujah and Barkhof, Frederik and van de Giessen, Elsmarieke and Biessels, Geert Jan and Teunissen, Charlotte Elisabeth 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 = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz70856_104832},
url = {https://doi.org/10.1002/alz70856_104832}
}
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Key findings
- Result NfL levels increased stepwise from A‐V‐ to A+V+ groups, suggesting an additive effect of amyloid and vascular pathologies (Figure 1).
- Subsequent regression analysis revealed SVD score as a significant predictor of NfL levels, while amyloid status was not (Model 1 and 2, Table 1).
- An interaction term revealed that amyloid status moderated the effect of SVD score on NfL levels (Model 3).
- Stratified analysis showed higher baseline NfL levels in amyloid‐positive individuals, with SVD score remaining a significant predictor in both groups.
- These results underscore the importance of considering multiple pathologies when interpreting NfL as a neurodegeneration biomarker in memory clinic settings.
Why it matters
In this memory clinic group, plasma neurofilament light increased stepwise from those with neither amyloid nor vascular pathology to those with both, suggesting an additive effect. Regression analysis found small vessel disease score, but not amyloid status, significantly predicted neurofilament light levels, and amyloid status moderated the effect of small vessel disease.
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Study details
- Participants371
- Evidence strengthModerate
How this study scored 39/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 371 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 | 2 / 4 | Last-listed author Argonde C. van Harten: h-index 24 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University Medical Center Utrecht: institution h-index 1,076 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 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 |
| Total | 39 / 100 | — |
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