Home › Research › Biomarkers
Association of Apolipoprotein E ɛ4 Allele With Clinical and Multimodal Biomarker Changes of Alzheimer Disease in Adults With Down Syndrome
Bejanin A, Iulita MF, Vilaplana E, Carmona-Iragui M, Benejam B, Videla L, Barroeta I, Fernandez S et al.. JAMA neurology, 2021-08-01
Topic: Amyloid, tau and blood-test diagnosis
Previous studies have suggested that the APOE ɛ4 allele plays a role in the risk and age at onset of dementia in DS; however, data on in vivo biomarkers remain scarce. Results Of the 464 adults with DS included in the study, 97 (20.9%) were APOE ɛ4 allele carriers and 367 (79.1%) were noncarriers. APOE ɛ4 allele carriers compared with noncarriers presented with AD symptoms at a younger age (mean [SD] age, 50.7 [4.4] years vs 52.7 [5.8] years; P = .02) and showed earlier cognitive decline. Conclusions and relevance In this study, the APOE ɛ4 allele was associated with earlier clinical and biomarker changes of AD in DS. These results provide insights into the mechanisms by which APOE increases the risk of AD, emphasizing the importance of APOE genotype for future clinical trials in DS.
Key findings
- Previous studies have suggested that the APOE ɛ4 allele plays a role in the risk and age at onset of dementia in DS; however, data on in vivo biomarkers remain scarce.
- Results Of the 464 adults with DS included in the study, 97 (20.9%) were APOE ɛ4 allele carriers and 367 (79.1%) were noncarriers.
- APOE ɛ4 allele carriers compared with noncarriers presented with AD symptoms at a younger age (mean [SD] age, 50.7 [4.4] years vs 52.7 [5.8] years; P = .02) and showed earlier cognitive decline.
- Conclusions and relevance In this study, the APOE ɛ4 allele was associated with earlier clinical and biomarker changes of AD in DS.
- These results provide insights into the mechanisms by which APOE increases the risk of AD, emphasizing the importance of APOE genotype for future clinical trials in DS.
Why it matters
In adults with Down syndrome, carrying the APOE ɛ4 allele was associated with earlier clinical and biomarker changes of Alzheimer's disease. It is an observational cohort study and does not test any treatment, cure or prevention.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designcohort study
- Effect size20.9%; 79.1%; 52.6%
- Evidence strengthModerate
How this study scored 64/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for sample size, studied in people 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 | 7 / 12 | A cohort study following people over time |
| 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 | 3 / 5 | 2021 — within 6 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 4 / 7 | Cited 77 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.0 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 4 / 6 | Cited 9.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 13 other studies in this library |
| Still being cited | 2 / 4 | Cited 46 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Juan Fortea: h-index 72 (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 21 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34228042) |
| Free to read | 2 / 2 | Free to read |
| Total | 64 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamaneurol.2021.1893
- PubMed: 34228042
- 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
Bejanin, A., Iulita, M. F., Vilaplana, E., Carmona-Iragui, M., Benejam, B., Videla, L., et al. (2021). Association of Apolipoprotein E ɛ4 Allele With Clinical and Multimodal Biomarker Changes of Alzheimer Disease in Adults With Down Syndrome. JAMA neurology. https://doi.org/10.1001/jamaneurol.2021.1893
Vancouver
Bejanin A, Iulita MF, Vilaplana E, Carmona-Iragui M, Benejam B, Videla L, et al. Association of Apolipoprotein E ɛ4 Allele With Clinical and Multimodal Biomarker Changes of Alzheimer Disease in Adults With Down Syndrome. JAMA neurology. 2021. doi:10.1001/jamaneurol.2021.1893. PMID: 34228042.
BibTeX
@article{bejanin2021-34228042,
author = {Bejanin, A. and Iulita, M. F. and Vilaplana, E. and Carmona-Iragui, M. and Benejam, B. and Videla, L. and Barroeta, I. and Fernandez, S. and others},
title = {{Association of Apolipoprotein E ɛ4 Allele With Clinical and Multimodal Biomarker Changes of Alzheimer Disease in Adults With Down Syndrome}},
journal = {JAMA neurology},
year = {2021},
doi = {10.1001/jamaneurol.2021.1893},
pmid = {34228042},
url = {https://doi.org/10.1001/jamaneurol.2021.1893}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 21.
Later studies that cite this one
13 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.