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CSF sAPPβ, YKL-40, and neurofilament light in frontotemporal lobar degeneration
Alcolea D, Vilaplana E, Suárez-Calvet M, Illán-Gala I, Blesa R, Clarimón J, Lladó A, Sánchez-Valle R et al.. Neurology, 2017-06-07
Topic: Brain proteins, microglia and lab models
Objective To analyze the clinical utility of 3 CSF biomarkers and their structural imaging correlates in a large cohort of patients with different dementia and parkinsonian syndromes within the spectrum of frontotemporal lobar degeneration (FTLD). Methods We analyzed 3 CSF biomarkers (YKL-40, soluble β fragment of amyloid precursor protein [sAPPβ], neurofilament light [NfL]) and core Alzheimer disease (AD) biomarkers (β-amyloid 1-42 , total tau, phosphorylated tau) in patients with FTLD-related clinical syndromes (n = 159): behavioral variant of frontotemporal dementia (n = 68), nonfluent (n = 23) and semantic (n = 19) variants of primary progressive aphasia, progressive supranuclear palsy (n = 28), and corticobasal syndrome (n = 21). We also included patients with AD (n = 72) and cognitively normal controls (CN; n = 76). We compared cross-sectional biomarker levels between groups, studied their correlation with cortical thickness, and evaluated their potential diagnostic utility. Results Patients with FTLD-related syndromes had lower levels of sAPPβ than CN and patients with AD. The levels of sAPPβ showed a strong correlation with cortical structural changes in frontal and cingulate areas. NfL and YKL-40 levels were high in both the FTLD and AD groups compared to controls. In the receiver operating characteristic analysis, the sAPPβ/YKL-40 and NfL/sAPPβ ratios had areas under the curve of 0.91 and 0.96, respectively, distinguishing patients with FTLD from CN, and of 0.84 and 0.85, distinguishing patients with FTLD from patients with AD. Conclusions The combination of sAPPβ with YKL-40 and with NfL in CSF could be useful to increase the certainty of the diagnosis of FTLD-related syndromes in clinical practice. Classification of evidence This study provides Class III evidence that CSF levels of sAPPβ, YKL-40, and NfL are useful to identify patients with FTLD-related syndromes.
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APA 7th
Alcolea, D., Vilaplana, E., Suárez-Calvet, M., Illán-Gala, I., Blesa, R., Clarimón, J., et al. (2017). CSF sAPPβ, YKL-40, and neurofilament light in frontotemporal lobar degeneration. Neurology. https://doi.org/10.1212/wnl.0000000000004088
Vancouver
Alcolea D, Vilaplana E, Suárez-Calvet M, Illán-Gala I, Blesa R, Clarimón J, et al. CSF sAPPβ, YKL-40, and neurofilament light in frontotemporal lobar degeneration. Neurology. 2017. doi:10.1212/wnl.0000000000004088. PMID: 28592456.
BibTeX
@article{alcolea2017-28592456,
author = {Alcolea, D. and Vilaplana, E. and Suárez-Calvet, M. and Illán-Gala, I. and Blesa, R. and Clarimón, J. and Lladó, A. and Sánchez-Valle, R. and others},
title = {{CSF sAPPβ, YKL-40, and neurofilament light in frontotemporal lobar degeneration}},
journal = {Neurology},
year = {2017},
doi = {10.1212/wnl.0000000000004088},
pmid = {28592456},
url = {https://doi.org/10.1212/wnl.0000000000004088}
}
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Key findings
- Results Patients with FTLD-related syndromes had lower levels of sAPPβ than CN and patients with AD.
- NfL and YKL-40 levels were high in both the FTLD and AD groups compared to controls.
Why it matters
In this cross-sectional study, people with frontotemporal lobar degeneration-related syndromes had lower CSF sAPPβ than controls and people with Alzheimer's disease, while NfL and YKL-40 were high in both disease groups. These are biomarker differences for diagnosis, not evidence of a treatment, cure, or prevention.
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Study details
- Study designcross-sectional
- Participants159
- Evidence strengthModerate
How this study scored 61/100
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 (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 2 / 5 | 2017 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 159 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 | 5 / 7 | Cited 124 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.3 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 4 / 6 | Cited 11.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 12 other studies in this library |
| Still being cited | 2 / 4 | Cited 22 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Alberto Lleó: h-index 92 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Universitat Autònoma de Barcelona: institution h-index 782 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28592456) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 61 / 100 | — |
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May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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