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Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome-Alzheimer’s disease
Farrell C, Buhidma Y, Mumford P, Heywood WE, Hällqvist J, Flores-Aguilar L, Andrews E, Rahimzadah N et al.. Acta neuropathologica, 2025-02-25
Topic: Genetics and APOE
Trisomy of chromosome 21, the cause of Down syndrome (DS), is the most commonly occurring genetic cause of Alzheimer’s disease (AD). Here, we compare the frontal cortex proteome of people with Down syndrome-Alzheimer’s disease (DSAD) to demographically matched cases of early-onset AD and healthy ageing controls. We find wide dysregulation of the proteome, beyond proteins encoded by chromosome 21, including an increase in the abundance of the key AD-associated protein, APOE, in people with DSAD compared to matched cases of AD. To understand the cell types that may contribute to changes in protein abundance, we undertook a matched single-nuclei RNA-sequencing study, which demonstrated that APOE expression was elevated in subtypes of astrocytes, endothelial cells and pericytes in DSAD. We further investigate how trisomy 21 may cause increased APOE. Increased abundance of APOE may impact the development of, or response to, AD pathology in the brain of people with DSAD, altering disease mechanisms with clinical implications. Overall, these data highlight that trisomy 21 alters both the transcriptome and proteome of people with DS in the context of AD, and that these differences should be considered when selecting therapeutic strategies for this vulnerable group of individuals who have high-risk of early-onset dementia.
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APA 7th
Farrell, C., Buhidma, Y., Mumford, P., Heywood, W. E., Hällqvist, J., Flores-Aguilar, L., et al. (2025). Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome-Alzheimer’s disease. Acta neuropathologica. https://doi.org/10.1101/2025.02.24.639862
Vancouver
Farrell C, Buhidma Y, Mumford P, Heywood WE, Hällqvist J, Flores-Aguilar L, et al. Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome-Alzheimer’s disease. Acta neuropathologica. 2025. doi:10.1101/2025.02.24.639862.
BibTeX
@article{farrell2025-39d43f22,
author = {Farrell, C. and Buhidma, Y. and Mumford, P. and Heywood, W. E. and Hällqvist, J. and Flores-Aguilar, L. and Andrews, E. and Rahimzadah, N. and others},
title = {{Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome-Alzheimer’s disease}},
journal = {Acta neuropathologica},
year = {2025},
doi = {10.1101/2025.02.24.639862},
url = {https://doi.org/10.1101/2025.02.24.639862}
}
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Key findings
- We find wide dysregulation of the proteome, beyond proteins encoded by chromosome 21, including an increase in the abundance of the key AD-associated protein, APOE, in people with DSAD compared to matched cases of AD.
- To understand the cell types that may contribute to changes in protein abundance, we undertook a matched single-nuclei RNA-sequencing study, which demonstrated that APOE expression was elevated in subtypes of astrocytes, endothelial cells and pericytes in DSAD.
- Overall, these data highlight that trisomy 21 alters both the transcriptome and proteome of people with DS in the context of AD, and that these differences should be considered when selecting therapeutic strategies for this vulnerable group of individuals who have high-risk of early-onset dementia.
Study details
- Evidence strengthLow
How this study scored 47/100
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 and multi-centre collaboration, so those were left out: it earned 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Acta neuropathologica) |
| 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 | 2025 — 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
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