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Lecanemab and Vascular-Amyloid Deposition in Brains of People With Down Syndrome
Liu L, Saba A, Pascual JR, Miller MB, Hennessey EL, Lott IT, Brickman AM, Wilcock DM et al.. JAMA neurology, 2024-10-01
Topic: Brain proteins, microglia and lab models
Importance Anti-β-amyloid immunotherapy using lecanemab is becoming increasingly available to patients with Alzheimer disease (AD). Individuals with Down syndrome (DS) develop AD neuropathology by age 40 years, representing a significant cohort of genetically determined AD. Objective To investigate the binding properties of lecanemab in the brains of people with DS, in anticipation of their inclusion in clinical trials or access to antiamyloid immunotherapies. Design, setting, participants The study included cases of postmortem brain tissue analysis from 15 individuals with DS aged 43 to 68 years that were acquired from Alzheimer Disease research centers at the University of California, Irvine and the University of Kentucky from 2008 to 2021. Data were analyzed from August 2023 through May 2024. Exposure The binding properties of lecanemab were assessed in brain tissue. Main outcome The primary outcome was the extent of lecanemab binding to amyloid plaques and brain blood vessels. Results Tissue from 15 people (8 were female [53%]) with DS ranging in age from 43 to 68 (mean, 56.6) years were included in the study. Lecanemab-labeled amyloid plaques appeared in all 15 DS cases studied, indicating potential target engagement. However, extensive binding of lecanemab to brain blood vessels in DS was observed, raising significant safety concerns. These findings underscore the necessity for clinical trials of lecanemab in people with DS to evaluate both safety and efficacy, particularly in individuals older than 43 years. Conclusions and relevance These findings suggest significant binding of lecanemab to cerebral amyloid angiopathy in DS. Lecanemab should be rigorously tested in clinical trials for AD in the DS population to determine its safety and efficacy, especially in those older than 43 years.
Key findings
- Individuals with Down syndrome (DS) develop AD neuropathology by age 40 years, representing a significant cohort of genetically determined AD.
- Results Tissue from 15 people (8 were female [53%]) with DS ranging in age from 43 to 68 (mean, 56.6) years were included in the study.
- However, extensive binding of lecanemab to brain blood vessels in DS was observed, raising significant safety concerns.
- These findings underscore the necessity for clinical trials of lecanemab in people with DS to evaluate both safety and efficacy, particularly in individuals older than 43 years.
- Conclusions and relevance These findings suggest significant binding of lecanemab to cerebral amyloid angiopathy in DS.
Why it matters
In postmortem brain tissue from 15 people with Down syndrome, the Alzheimer's drug lecanemab bound to amyloid plaques but also bound extensively to brain blood vessels, which raises safety concerns. The authors say clinical trials are needed to evaluate whether lecanemab is safe in people with Down syndrome.
Study details
- Participants15
- Evidence strengthModerate
How this study scored 53/100
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 (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (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 | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 15 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 | 3 / 7 | Cited 26 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.5 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 3 / 6 | Cited 6.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 26 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Elizabeth Head: h-index 98 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39158850) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 53 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamaneurol.2024.2579
- PubMed: 39158850
- Original source →
- Free full text: PubMed Central →
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
Liu, L., Saba, A., Pascual, JR., Miller, M. B., Hennessey, E. L., Lott, I. T., et al. (2024). Lecanemab and Vascular-Amyloid Deposition in Brains of People With Down Syndrome. JAMA neurology. https://doi.org/10.1001/jamaneurol.2024.2579
Vancouver
Liu L, Saba A, Pascual JR, Miller MB, Hennessey EL, Lott IT, et al. Lecanemab and Vascular-Amyloid Deposition in Brains of People With Down Syndrome. JAMA neurology. 2024. doi:10.1001/jamaneurol.2024.2579. PMID: 39158850.
BibTeX
@article{liu2024-39158850,
author = {Liu, L. and Saba, A. and Pascual, JR. and Miller, M. B. and Hennessey, E. L. and Lott, I. T. and Brickman, A. M. and Wilcock, D. M. and others},
title = {{Lecanemab and Vascular-Amyloid Deposition in Brains of People With Down Syndrome}},
journal = {JAMA neurology},
year = {2024},
doi = {10.1001/jamaneurol.2024.2579},
pmid = {39158850},
url = {https://doi.org/10.1001/jamaneurol.2024.2579}
}
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