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CSF sAPPβ, YKL-40, and NfL along the ALS-FTD spectrum
Illán-Gala I, Alcolea D, Montal V, Dols-Icardo O, Muñoz L, de Luna N, Turón-Sans J, Cortés-Vicente E et al.. Neurology, 2018-10-05
Topic: Brain proteins, microglia and lab models
Objective To investigate the clinical utility of 3 CSF biomarkers along the clinical spectrum of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Methods We analyzed 3 CSF biomarkers: the soluble β-fragment of amyloid precursor protein (sAPPβ), YKL-40, and neurofilament light (NfL) in FTD (n = 86), ALS (n = 38), and a group of age-matched cognitively normal controls (n = 49). Participants with FTD with a CSF profile of Alzheimer disease were excluded. We compared cross-sectional biomarker levels between groups, studied their correlation with cognitive and functional scales (global cognitive z score, frontotemporal lobar degeneration Clinical Dementia Rating, revised ALS Functional Rating Scale, and ALS progression rate), survival, and cortical thickness. Results We found increased levels of YKL-40 and decreased levels of sAPPβ in both FTD and ALS groups compared to controls. The lowest sAPPβ levels and sAPPβ/YKL-40 ratio were found in the FTD group. In FTD, sAPPβ and the sAPPβ/YKL-40 ratio correlated with the disease severity. In the whole ALS-FTD spectrum, NfL levels and the NfL:sAPPβ ratio correlated with global cognitive performance ( r = -0.41, p r = -0.44, p r = 0.51, p = 0.001) and was independently associated with shorter survival. In both FTD and ALS groups, the sAPPβ/YKL-40 ratio showed a positive correlation with cortical thickness in frontotemporal regions. Conclusions sAPPβ, YKL-40, and NfL could represent valuable tools for the staging and prognosis of patients within the ALS-FTD clinical spectrum. Classification of evidence This study provides Class III evidence that CSF levels of sAPPβ, YKL-40, and NfL are useful to assess frontotemporal neurodegeneration and the progression rate in the ALS-FTD continuum.
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APA 7th
Illán-Gala, I., Alcolea, D., Montal, V., Dols-Icardo, O., Muñoz, L., de Luna, N., et al. (2018). CSF sAPPβ, YKL-40, and NfL along the ALS-FTD spectrum. Neurology. https://doi.org/10.1212/wnl.0000000000006383
Vancouver
Illán-Gala I, Alcolea D, Montal V, Dols-Icardo O, Muñoz L, de Luna N, et al. CSF sAPPβ, YKL-40, and NfL along the ALS-FTD spectrum. Neurology. 2018. doi:10.1212/wnl.0000000000006383. PMID: 30291183.
BibTeX
@article{illangala2018-30291183,
author = {Illán-Gala, I. and Alcolea, D. and Montal, V. and Dols-Icardo, O. and Muñoz, L. and de Luna, N. and Turón-Sans, J. and Cortés-Vicente, E. and others},
title = {{CSF sAPPβ, YKL-40, and NfL along the ALS-FTD spectrum}},
journal = {Neurology},
year = {2018},
doi = {10.1212/wnl.0000000000006383},
pmid = {30291183},
url = {https://doi.org/10.1212/wnl.0000000000006383}
}
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Key findings
- Results We found increased levels of YKL-40 and decreased levels of sAPPβ in both FTD and ALS groups compared to controls.
- In the whole ALS-FTD spectrum, NfL levels and the NfL:sAPPβ ratio correlated with global cognitive performance ( r = -0.41, p r = -0.44, p r = 0.51, p = 0.001) and was independently associated with shorter survival.
Why it matters
In spinal-fluid samples from 86 people with frontotemporal dementia, 38 with ALS and 49 healthy controls, both patient groups had higher YKL-40 and lower sAPPβ than controls, and the sAPPβ/YKL-40 ratio tracked disease severity in FTD and brain thickness in frontotemporal regions. Neurofilament light (NfL) levels were linked to poorer thinking scores across the ALS-FTD spectrum. These are group-level associations in people whose spinal fluid did not look like Alzheimer's; the study tested no treatment and does not show these markers diagnose or predict Alzheimer's disease.
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Study details
- Study designcross-sectional
- Participants86
- 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 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 | 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 | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 1 / 4 | 86 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 | 4 / 7 | Cited 85 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.5 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 3 / 6 | Cited 6.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 2 / 4 | Cited 26 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 30291183) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 55 / 100 | — |
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