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Identifying Genetic Risk for Amyloid-Related Imaging Abnormalities
John Hardy, Jonathan M Schott. Neurology, 2023-12-28
Topic: Plasma and spinal-fluid biomarkers
In the last 2 years, there have been 3 successful trials of antiamyloid antibodies in Alzheimer disease (AD): aducanemab, now controversially US Food and Drug Administration-approved under the accelerated approval pathway1; lecanemab, now FDA-approved2; and donanemab, now going through the approval process.3 All 3 share a common broad mechanism, that is, antibody-mediated removal of β-amyloid (Aβ) from the brain, and this is almost certainly the basis of their therapeutic action.4 When used in the earliest symptomatic stages of AD, all have modest clinical effects, all clear Aβ from the brain, and all show evidence for some changes in molecular markers believed to be downstream of Aβ accumulation in keeping with disease modification.4 However, all these drugs-and several other antiamyloid immunotherapies that failed to show positive effects in clinical trials (e.g. bapineuzemab and gantenerumab)5,6-have the troubling adverse event of antibody-related imaging abnormalities (ARIA). ARIA can take the form of vasogenic edema or sulcal effusion (ARIA-E) or haemosiderin deposition due to hemorrhage (ARIA-H).7 In vivo, ARIA is detected using MRI: ARIA-E is visible on fluid attenuation inversion recovery sequences; ARIA-H is best seen on iron-sensitive (T2* or susceptibility-weighted imaging) as microbleeds and/or superficial hemosiderin deposition. The pathophysiology of ARIA has yet to be fully determined but may result from antibody-mediated breakdown of amyloid plaques releasing Aβ which is deposited in vessels leading to increased cerebral amyloid angiopathy or alterations in perivascular clearance or inflammation, possibly through complement activation.8.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Hardy, J., & Schott, J. M. (2024). Identifying Genetic Risk for Amyloid-Related Imaging Abnormalities. Neurology. https://doi.org/10.1212/wnl.0000000000208096
Vancouver
Hardy J, Schott JM. Identifying Genetic Risk for Amyloid-Related Imaging Abnormalities. Neurology. 2024. doi:10.1212/wnl.0000000000208096. PMID: 38165303.
BibTeX
@article{hardy2024-38165303,
author = {Hardy, John and Schott, Jonathan M},
title = {{Identifying Genetic Risk for Amyloid-Related Imaging Abnormalities}},
journal = {Neurology},
year = {2024},
doi = {10.1212/wnl.0000000000208096},
pmid = {38165303},
url = {https://doi.org/10.1212/wnl.0000000000208096}
}
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Key findings
- The pathophysiology of ARIA has yet to be fully determined but may result from antibody-mediated breakdown of amyloid plaques releasing Aβ which is deposited in vessels leading to increased cerebral amyloid angiopathy or alterations in perivascular clearance or inflammation, possibly through complement activation.8.
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Study details
- Evidence strengthLow
How this study scored 46/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 26 of the 56 points we could judge it on, which is 46 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38165303) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 26 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 26 of the 56 points we could judge it on is 46 out of 100. |
| Total | 46 / 100 | — |
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