Home › Research › Biomarkers
Biomarker pattern of ARIA-E participants in phase 3 randomized clinical trials with bapineuzumab
Liu E, Wang D, Sperling R, Salloway S, Fox NC, Blennow K, Scheltens P, Schmidt ME et al.. Neurology, 2018-02-02
Topic: Amyloid, tau and blood-test diagnosis
Objective To evaluate whether amyloid-related imaging abnormalities with edema/effusion (ARIA-E) observed in bapineuzumab clinical trials was associated with specific biomarker patterns. Methods Bapineuzumab, an anti-β-amyloid monoclonal antibody, was evaluated in patients with mild to moderate Alzheimer disease. Amyloid PET imaging, CSF biomarkers, or volumetric MRI (vMRI) were assessed. Results A total of 1,512 participants underwent one or more biomarker assessments; 154 developed incident ARIA-E. No differences were observed at baseline between ARIA-E and non-ARIA-E participants in brain amyloid burden by PET, the majority of vMRI measures, or CSF biomarkers, with the exception of lower baseline CSF Aβ 42 in APOE ε4 noncarrier ARIA-E vs non-ARIA-E groups (bapineuzumab non-ARIA-E p = 0.027; placebo non-ARIA-E p = 0.012). At week 71, bapineuzumab-treated participants with ARIA-E vs non-ARIA-E showed greater reduction in brain amyloid PET, greater reductions in CSF phosphorylated tau (p-tau) (all comparisons p p p 40 concentrations was observed for ARIA-E versus both non-ARIA-E groups (bapineuzumab/placebo non-ARIA-E p = 0.015/0.049). No group differences were observed at week 71 for changes in whole brain volume or CSF Aβ 42 . Conclusions Baseline biomarkers largely do not predict risk for developing ARIA-E. ARIA-E was associated with significant longitudinal changes in several biomarkers, with larger reductions in amyloid PET and CSF p-tau and t-tau concentrations, and paradoxically greater hippocampal volume reduction and ventricular enlargement, suggesting that ARIA-E in bapineuzumab-treated cases may be related to increased Aβ efflux from the brain and affecting downstream pathogenic processes.
Key findings
- Objective To evaluate whether amyloid-related imaging abnormalities with edema/effusion (ARIA-E) observed in bapineuzumab clinical trials was associated with specific biomarker patterns.
- Results A total of 1,512 participants underwent one or more biomarker assessments; 154 developed incident ARIA-E.
- At week 71, bapineuzumab-treated participants with ARIA-E vs non-ARIA-E showed greater reduction in brain amyloid PET, greater reductions in CSF phosphorylated tau (p-tau) (all comparisons p < 0.01), and total tau (t-tau) (all comparisons p < 0.025), and greater hippocampal volume reduction and ventricular enlargement (all p < 0.05).
- ARIA-E was associated with significant longitudinal changes in several biomarkers, with larger reductions in amyloid PET and CSF p-tau and t-tau concentrations, and paradoxically greater hippocampal volume reduction and ventricular enlargement, suggesting that ARIA-E in bapineuzumab-treated cases may be related to increased Aβ efflux from the brain and affecting downstream pathogenic processes.
Why it matters
In phase 3 bapineuzumab trials (1,512 people with mild to moderate Alzheimer's who had biomarker tests; 154 developed brain swelling called ARIA-E), baseline amyloid PET, CSF and MRI measures largely did not predict who would develop ARIA-E. By week 71, treated participants with ARIA-E showed larger drops in amyloid PET and CSF p-tau and t-tau, but also "paradoxically greater hippocampal volume reduction and ventricular enlargement". The authors suggest ARIA-E may reflect increased amyloid clearance from the brain. This is a biomarker comparison, not a randomized one, and it does not show that bapineuzumab or ARIA-E benefits patients.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designlongitudinal study
- Participants1,512
- Evidence strengthModerate
How this study scored 68/100
Published in a leading specialty journal, and it is a large phase 3 trial. Scored zero for effect reported because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 65 of the 96 points we could judge it on, which is 68 out of 100.
| 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 | 11 / 12 | A large phase 3 trial (from PubMed type “Clinical Trial, Phase III”) |
| 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 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,512 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 | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 4 / 7 | Cited 44 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.4 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 2 / 6 | Cited 1.9× 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 15 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author H. Chehrenama holds only 1 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29429971) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 65 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 65 of the 96 points we could judge it on is 68 out of 100. |
| Total | 68 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1212/wnl.0000000000005060
- PubMed: 29429971
- Original source →
- Free full text: discovery.ucl.ac.uk →
Full text: free to read — Unpaywall 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
Liu, E., Wang, D., Sperling, R., Salloway, S., Fox, N. C., Blennow, K., et al. (2018). Biomarker pattern of ARIA-E participants in phase 3 randomized clinical trials with bapineuzumab. Neurology. https://doi.org/10.1212/wnl.0000000000005060
Vancouver
Liu E, Wang D, Sperling R, Salloway S, Fox NC, Blennow K, et al. Biomarker pattern of ARIA-E participants in phase 3 randomized clinical trials with bapineuzumab. Neurology. 2018. doi:10.1212/wnl.0000000000005060. PMID: 29429971.
BibTeX
@article{liu2018-29429971,
author = {Liu, E. and Wang, D. and Sperling, R. and Salloway, S. and Fox, N. C. and Blennow, K. and Scheltens, P. and Schmidt, M. E. and others},
title = {{Biomarker pattern of ARIA-E participants in phase 3 randomized clinical trials with bapineuzumab}},
journal = {Neurology},
year = {2018},
doi = {10.1212/wnl.0000000000005060},
pmid = {29429971},
url = {https://doi.org/10.1212/wnl.0000000000005060}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 17.
Later studies that cite this one
7 studies in the alzhub library list this one in their references.
Related studies in Biomarkers
Also tagged “double-blind”
783 studies in the library carry the topic tag “double-blind”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 783 tagged studies.