Home › Research › Biomarkers
Use of amyloid-PET to determine cutpoints for CSF markers: A multicenter study
Zwan MD, Rinne JO, Hasselbalch SG, Nordberg A, Lleó A, Herukka SK, Soininen H, Law I et al.. Neurology, 2015-10-14
Topic: Amyloid, tau and blood-test diagnosis
Objectives To define CSF β-amyloid 1-42 (Aβ42) cutpoints to detect cortical amyloid deposition as assessed by 11C-Pittsburgh compound B ([11C]PiB)-PET and to compare these calculated cutpoints with cutpoints currently used in clinical practice. Methods We included 433 participants (57 controls, 99 with mild cognitive impairment, 195 with Alzheimer disease [AD] dementia, and 82 with non-AD dementia) from 5 European centers. We calculated for each center and for the pooled cohort CSF Aβ42 and Aβ42/tau ratio cutpoints for cortical amyloid deposition based on visual interpretation of [11C]PiB-PET images. Results Amyloid-PET-based calculated CSF Aβ42 cutpoints ranged from 521 to 616 pg/mL, whereas existing clinical-based cutpoints ranged from 400 to 550 pg/mL. Using the calculated cutpoint from the pooled sample (557 pg/mL), concordance between CSF Aβ42 and amyloid-PET was 84%. Similar concordance was found when using a dichotomized Aβ42/tau ratio. Exploratory analysis showed that participants with a positive amyloid-PET and normal CSF Aβ42 levels had higher CSF tau and phosphorylated tau levels and more often had mild cognitive impairment or AD dementia compared with participants who had negative amyloid-PET and abnormal CSF Aβ42 levels. Conclusions Amyloid-PET-based CSF Aβ42 cutpoints were higher and tended to reduce intercenter variability compared with clinical-based cutpoints. Discordant participants with normal CSF Aβ42 and a positive amyloid-PET may be more likely to have AD-related amyloid pathology than participants with abnormal CSF Aβ42 and a negative amyloid-PET. Classification of evidence This study provides Class II evidence that an amyloid-PET-based CSF Aβ42 cutpoint identifies individuals with amyloid deposition with a sensitivity of 87% and specificity of 80%.
Key findings
- Results Amyloid-PET-based calculated CSF Aβ42 cutpoints ranged from 521 to 616 pg/mL, whereas existing clinical-based cutpoints ranged from 400 to 550 pg/mL.
- Exploratory analysis showed that participants with a positive amyloid-PET and normal CSF Aβ42 levels had higher CSF tau and phosphorylated tau levels and more often had mild cognitive impairment or AD dementia compared with participants who had negative amyloid-PET and abnormal CSF Aβ42 levels.
- Conclusions Amyloid-PET-based CSF Aβ42 cutpoints were higher and tended to reduce intercenter variability compared with clinical-based cutpoints.
Why it matters
Across 433 people at 5 European centers, spinal-fluid amyloid (CSF Aβ42) cut-offs set against amyloid PET scans were higher (521–616 pg/mL) than the cut-offs clinics were using (400–550 pg/mL), and they varied less from center to center. At the pooled cut-off of 557 pg/mL, the fluid test and the scan agreed for 84% of participants, so roughly 1 in 6 got a different answer from each test. This is a diagnostic study. It does not report any treatment, cure or prevention of Alzheimer's disease.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Participants433
- Evidence strengthModerate
How this study scored 52/100
Published in a leading specialty journal. Scored zero for study design, 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 | 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 | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 433 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 66 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.5 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 3 / 6 | Cited 6.8× 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 | 1 / 4 | Cited 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Pieter Jelle Visser: h-index 90 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Amsterdam UMC Location Vrije Universiteit Amsterdam: institution h-index 938 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26468410) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1212/wnl.0000000000002081
- PubMed: 26468410
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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
Zwan, M. D., Rinne, J. O., Hasselbalch, S. G., Nordberg, A., Lleó, A., Herukka, S. K., et al. (2016). Use of amyloid-PET to determine cutpoints for CSF markers: A multicenter study. Neurology. https://doi.org/10.1212/wnl.0000000000002081
Vancouver
Zwan MD, Rinne JO, Hasselbalch SG, Nordberg A, Lleó A, Herukka SK, et al. Use of amyloid-PET to determine cutpoints for CSF markers: A multicenter study. Neurology. 2016. doi:10.1212/wnl.0000000000002081. PMID: 26468410.
BibTeX
@article{zwan2016-26468410,
author = {Zwan, M. D. and Rinne, J. O. and Hasselbalch, S. G. and Nordberg, A. and Lleó, A. and Herukka, S. K. and Soininen, H. and Law, I. and others},
title = {{Use of amyloid-PET to determine cutpoints for CSF markers: A multicenter study}},
journal = {Neurology},
year = {2016},
doi = {10.1212/wnl.0000000000002081},
pmid = {26468410},
url = {https://doi.org/10.1212/wnl.0000000000002081}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 22.
Later studies that cite this one
7 studies in the alzhub library list this one in their references.
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.