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Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study
Leuzy A, Chiotis K, Hasselbalch SG, Rinne JO, de Mendonça A, Otto M, Lleó A, Castelo-Branco M et al.. Brain : a journal of neurology, 2016-07-07
Topic: Brain proteins, microglia and lab models
The aim of this study was to assess the agreement between data on cerebral amyloidosis, derived using Pittsburgh compound B positron emission tomography and (i) multi-laboratory INNOTEST enzyme linked immunosorbent assay derived cerebrospinal fluid concentrations of amyloid-β42; (ii) centrally measured cerebrospinal fluid amyloid-β42 using a Meso Scale Discovery enzyme linked immunosorbent assay; and (iii) cerebrospinal fluid amyloid-β42 centrally measured using an antibody-independent mass spectrometry-based reference method. Moreover, we examined the hypothesis that discordance between amyloid biomarker measurements may be due to interindividual differences in total amyloid-β production, by using the ratio of amyloid-β42 to amyloid-β40 Our study population consisted of 243 subjects from seven centres belonging to the Biomarkers for Alzheimer's and Parkinson's Disease Initiative, and included subjects with normal cognition and patients with mild cognitive impairment, Alzheimer's disease dementia, frontotemporal dementia, and vascular dementia. All had Pittsburgh compound B positron emission tomography data, cerebrospinal fluid INNOTEST amyloid-β42 values, and cerebrospinal fluid samples available for reanalysis. Cerebrospinal fluid samples were reanalysed (amyloid-β42 and amyloid-β40) using Meso Scale Discovery electrochemiluminescence enzyme linked immunosorbent assay technology, and a novel, antibody-independent, mass spectrometry reference method. Pittsburgh compound B standardized uptake value ratio results were scaled using the Centiloid method. Concordance between Meso Scale Discovery/mass spectrometry reference measurement procedure findings and Pittsburgh compound B was high in subjects with mild cognitive impairment and Alzheimer's disease, while more variable results were observed for cognitively normal and non-Alzheimer's disease groups. Agreement between Pittsburgh compound B classification and Meso Scale Discovery/mass spectrometry reference measurement procedure findings was further improved when using amyloid-β42/40 Agreement between Pittsburgh compound B visual ratings and Centiloids was near complete. Despite improved agreement between Pittsburgh compound B and centrally analysed cerebrospinal fluid, a minority of subjects showed discordant findings. While future studies are needed, our results suggest that amyloid biomarker results may not be interchangeable in some individuals.
Key findings
- Pittsburgh compound B standardized uptake value ratio results were scaled using the Centiloid method.
- Concordance between Meso Scale Discovery/mass spectrometry reference measurement procedure findings and Pittsburgh compound B was high in subjects with mild cognitive impairment and Alzheimer's disease, while more variable results were observed for cognitively normal and non-Alzheimer's disease groups.
- While future studies are needed, our results suggest that amyloid biomarker results may not be interchangeable in some individuals.
Why it matters
This multicentre study compared amyloid measured by Pittsburgh compound B PET imaging with several cerebrospinal fluid amyloid-β42 methods in people with normal cognition, mild cognitive impairment and various dementias. Agreement was high in mild cognitive impairment and Alzheimer's disease but more variable in cognitively normal and non-Alzheimer's groups, so these amyloid biomarkers may not always agree.
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Study details
- Participants243
- Evidence strengthLow
How this study scored 59/100
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 (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (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 | 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 | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 243 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 131 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.9 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 4 / 6 | Cited 14.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 other studies in this library |
| Still being cited | 2 / 4 | Cited 20 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Agneta K. Nordberg: h-index 103 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 23 institution(s) in 7 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27401520) |
| Free to read | 2 / 2 | Free to read |
| Total | 59 / 100 | — |
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Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Leuzy, A., Chiotis, K., Hasselbalch, S. G., Rinne, J. O., de Mendonça, A., Otto, M., et al. (2016). Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study. Brain : a journal of neurology. https://doi.org/10.1093/brain/aww160
Vancouver
Leuzy A, Chiotis K, Hasselbalch SG, Rinne JO, de Mendonça A, Otto M, et al. Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study. Brain : a journal of neurology. 2016. doi:10.1093/brain/aww160. PMID: 27401520.
BibTeX
@article{leuzy2016-27401520,
author = {Leuzy, A. and Chiotis, K. and Hasselbalch, S. G. and Rinne, J. O. and de Mendonça, A. and Otto, M. and Lleó, A. and Castelo-Branco, M. and others},
title = {{Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study}},
journal = {Brain : a journal of neurology},
year = {2016},
doi = {10.1093/brain/aww160},
pmid = {27401520},
url = {https://doi.org/10.1093/brain/aww160}
}
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