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Proteomic analysis of Down syndrome cerebrospinal fluid compared to late-onset and autosomal dominant Alzheimer´s disease
Montoliu-Gaya L, Bian S, Dammer EB, Alcolea D, Sauer M, Martá-Ariza M, Ashton NJ, Belbin O et al.. Nature communications, 2025-07-01
Topic: Brain proteins, microglia and lab models
Almost all individuals with Down Syndrome (DS) develop Alzheimer's disease (AD) by mid to late life. However, the degree to which AD in DS shares pathological changes with sporadic late-onset AD (LOAD) and autosomal dominant AD (ADAD) beyond core AD biomarkers such as amyloid-β (Aβ) and tau is unknown. Here, we used proteomics of cerebrospinal fluid from individuals with DS (n = 229) in the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) cohort to assess the evolution of AD pathophysiology from asymptomatic to dementia stages and compared the proteomic biomarker changes in DS to those observed in LOAD and ADAD. Although many proteomic alterations were shared across DS, LOAD, and ADAD, DS demonstrated more severe changes in immune-related proteins, extracellular matrix pathways, and plasma proteins likely related to blood-brain barrier dysfunction compared to LOAD. These changes were present in young adults with DS prior to the onset of Aβ or tau pathology, suggesting they are associated with trisomy 21 and may serve as risk factors for DSAD. DSAD showed an earlier increase in markers of axonal and white matter pathology and earlier changes in markers potentially associated with cerebral amyloid angiopathy compared to ADAD. The unique features of DSAD may have important implications for treatment strategies in this population.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Montoliu-Gaya, L., Bian, S., Dammer, E. B., Alcolea, D., Sauer, M., Martá-Ariza, M., et al. (2025). Proteomic analysis of Down syndrome cerebrospinal fluid compared to late-onset and autosomal dominant Alzheimer´s disease. Nature communications. https://doi.org/10.1038/s41467-025-61054-z
Vancouver
Montoliu-Gaya L, Bian S, Dammer EB, Alcolea D, Sauer M, Martá-Ariza M, et al. Proteomic analysis of Down syndrome cerebrospinal fluid compared to late-onset and autosomal dominant Alzheimer´s disease. Nature communications. 2025. doi:10.1038/s41467-025-61054-z. PMID: 40595720.
BibTeX
@article{montoliugaya2025-40595720,
author = {Montoliu-Gaya, L. and Bian, S. and Dammer, E. B. and Alcolea, D. and Sauer, M. and Martá-Ariza, M. and Ashton, N. J. and Belbin, O. and others},
title = {{Proteomic analysis of Down syndrome cerebrospinal fluid compared to late-onset and autosomal dominant Alzheimer´s disease}},
journal = {Nature communications},
year = {2025},
doi = {10.1038/s41467-025-61054-z},
pmid = {40595720},
url = {https://doi.org/10.1038/s41467-025-61054-z}
}
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.
Key findings
- Although many proteomic alterations were shared across DS, LOAD, and ADAD, DS demonstrated more severe changes in immune-related proteins, extracellular matrix pathways, and plasma proteins likely related to blood-brain barrier dysfunction compared to LOAD.
- These changes were present in young adults with DS prior to the onset of Aβ or tau pathology, suggesting they are associated with trisomy 21 and may serve as risk factors for DSAD.
- DSAD showed an earlier increase in markers of axonal and white matter pathology and earlier changes in markers potentially associated with cerebral amyloid angiopathy compared to ADAD.
Why it matters
This proteomic study of cerebrospinal fluid found that people with Down syndrome showed more severe changes in immune-related proteins, extracellular matrix pathways, and blood-brain barrier-related proteins compared to late-onset Alzheimer's disease, with some changes present before amyloid or tau pathology. The authors suggest these unique features may have implications for treatment strategies, but no treatment is tested here.
Study details
- Participants229
- Evidence strengthModerate
How this study scored 55/100
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 (Nature communications) |
| Journal's citation record | 4 / 4 | Nature Communications: journal h-index 747 (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 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 229 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 | 2 / 7 | Cited 13 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 7.1× 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 | 1 / 4 | Cited 13 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Erik C. B. Johnson: h-index 37 (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 11 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40595720) |
| Free to read | 2 / 2 | Free to read |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41467-025-61054-z
- PubMed: 40595720
- Original source →
- Free full text: Nature Communications →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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