Dissection of synaptic pathways through the CSF biomarkers for predicting Alzheimer disease
Tible M, Sandelius Å, Höglund K, Brinkmalm A, Cognat E, Dumurgier J, Zetterberg H, Hugon J et al.. Neurology, 2020-06-25
Topic: Amyloid, tau and blood-test diagnosis
Objective To assess the ability of a combination of synaptic CSF biomarkers to separate Alzheimer disease (AD) and non-AD disorders and to help in the differential diagnosis between neurocognitive diseases. Methods This was a retrospective cross-sectional monocentric study. All participants explored with CSF assessments for neurocognitive decline were invited to participate. After complete clinical and imaging evaluations, 243 patients were included. CSF synaptic (GAP-43, neurogranin, SNAP-25 total, SNAP-25aa40, synaptotagmin-1) and AD biomarkers were blindly quantified with ELISA or mass spectrometry. Statistical analysis compared CSF levels between the various groups of AD dementias (n = 81), mild cognitive impairment (MCI)-AD (n = 30), other MCI (n = 49), other dementias (OD) (n = 49), and neurologic controls (n = 35) and their discriminatory powers. Results All synaptic biomarkers were significantly increased in patients with MCI-AD and AD-dementia compared to the other groups. All synaptic biomarkers could efficiently discriminate AD dementias from OD (AUC ≥0.80). All but synaptotagmin were also able to discriminate patients with MCI-AD from controls (area under the curve [AUC] ≥0.85) and those with AD dementias from controls (AUC ≥0.80). Overall, CSF SNAP-25aa40 had the highest discriminative power (AUC 0.93 between patients with AD dementias and controls or OD, AUC 0.90 between those with MCI-AD and controls). Higher levels were associated with 2 alleles of APOE ε4. Conclusion All synaptic biomarkers tested had a good discriminatory power to distinguish patients with AD abnormal CSF from those with non-AD disorders. SNAP25aa40 demonstrated the highest power to discriminate AD CSF-positive patients from patients without AD and neurologic controls in this cohort. Classification of evidence This retrospective study provides Class II evidence that CSF synaptic biomarkers discriminate patients with AD from those without AD.
Key findings
- Results All synaptic biomarkers were significantly increased in patients with MCI-AD and AD-dementia compared to the other groups.
- Overall, CSF SNAP-25aa40 had the highest discriminative power (AUC 0.93 between patients with AD dementias and controls or OD, AUC 0.90 between those with MCI-AD and controls).
- Higher levels were associated with 2 alleles of APOE ε4.
- SNAP25aa40 demonstrated the highest power to discriminate AD CSF-positive patients from patients without AD and neurologic controls in this cohort.
Why it matters
This study found that several synaptic proteins measured in cerebrospinal fluid were increased in people with Alzheimer's disease and in those with mild cognitive impairment due to Alzheimer's, and could help tell these apart from other dementias. The authors report that one marker, SNAP-25aa40, had the highest ability to discriminate these groups.
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Study details
- Study designcross-sectional
- Participants81
- Effect sizeAUC 0.93; AUC 0.90
- Evidence strengthModerate
How this study scored 65/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for 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 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 1 / 4 | 81 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 10.6 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 4 / 6 | Cited 8.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 2 / 4 | Cited 33 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Kaj Blennow: h-index 220 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Inserm: institution h-index 1,988 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32586895) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 65 / 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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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
Tible, M., Å, S., Höglund, K., Brinkmalm, A., Cognat, E., Dumurgier, J., et al. (2020). Dissection of synaptic pathways through the CSF biomarkers for predicting Alzheimer disease. Neurology. https://doi.org/10.1212/wnl.0000000000010131
Vancouver
Tible M, Å S, Höglund K, Brinkmalm A, Cognat E, Dumurgier J, et al. Dissection of synaptic pathways through the CSF biomarkers for predicting Alzheimer disease. Neurology. 2020. doi:10.1212/wnl.0000000000010131. PMID: 32586895.
BibTeX
@article{tible2020-32586895,
author = {Tible, M. and Å, Sandelius and Höglund, K. and Brinkmalm, A. and Cognat, E. and Dumurgier, J. and Zetterberg, H. and Hugon, J. and others},
title = {{Dissection of synaptic pathways through the CSF biomarkers for predicting Alzheimer disease}},
journal = {Neurology},
year = {2020},
doi = {10.1212/wnl.0000000000010131},
pmid = {32586895},
url = {https://doi.org/10.1212/wnl.0000000000010131}
}
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