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The tau biomarker cascade is condensed in Down syndrome compared with sporadic Alzheimer's disease
Zammit MD, Bruzzone H, Cody KA, Morse J, Wilson R, Bettcher BT, McLachlan MJ, McVea AK et al.. Brain : a journal of neurology, 2026-07-01
Topic: Brain proteins, microglia and lab models
Characterizing the timing and progression of Alzheimer's disease biomarker onset in Down syndrome (DS) and contrasting potential timing differences with neurotypical adults is needed to identify optimal Alzheimer's disease therapeutic treatment windows in DS. In this study, 198 adults with DS from the Alzheimer Biomarker Consortium-Down Syndrome and 172 neurotypical adults from the Wisconsin Registry for Alzheimer's Prevention with available longitudinal beta-amyloid PET, tau PET and plasma p-tau217 analysed on the Lilly Meso Scale Delivery Platform were included. Individuals with DS had a significantly higher lifetime risk of beta-amyloid plaque onset. Temporal modelling of longitudinal biomarker measures revealed earlier age at positivity of beta-amyloid plaques, p-tau217 and neurofibrillary tau tangles in DS relative to the neurotypical cohort. The onset of p-tau217 and tau PET positivity in DS occurred nearly simultaneously, roughly 4-6 years following beta-amyloid onset, whereas the neurotypical group displayed greater temporal latency between positivity of the two biomarkers. The early and simultaneous onset of these biomarkers in DS highlights the necessity for early therapeutic interventions in this population. This work, combined with the upcoming anti-amyloid safety and efficacy clinical trials for DS will help to identify optimal treatment windows for these individuals.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Zammit, M. D., Bruzzone, H., Cody, K. A., Morse, J., Wilson, R., Bettcher, B. T., et al. (2026). The tau biomarker cascade is condensed in Down syndrome compared with sporadic Alzheimer's disease. Brain : a journal of neurology. https://doi.org/10.1093/brain/awaf428
Vancouver
Zammit MD, Bruzzone H, Cody KA, Morse J, Wilson R, Bettcher BT, et al. The tau biomarker cascade is condensed in Down syndrome compared with sporadic Alzheimer's disease. Brain : a journal of neurology. 2026. doi:10.1093/brain/awaf428. PMID: 41240365.
BibTeX
@article{zammit2026-41240365,
author = {Zammit, M. D. and Bruzzone, H. and Cody, K. A. and Morse, J. and Wilson, R. and Bettcher, B. T. and McLachlan, M. J. and McVea, A. K. and others},
title = {{The tau biomarker cascade is condensed in Down syndrome compared with sporadic Alzheimer's disease}},
journal = {Brain : a journal of neurology},
year = {2026},
doi = {10.1093/brain/awaf428},
pmid = {41240365},
url = {https://doi.org/10.1093/brain/awaf428}
}
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
- Individuals with DS had a significantly higher lifetime risk of beta-amyloid plaque onset.
- Temporal modelling of longitudinal biomarker measures revealed earlier age at positivity of beta-amyloid plaques, p-tau217 and neurofibrillary tau tangles in DS relative to the neurotypical cohort.
Why it matters
In adults with Down syndrome, beta-amyloid plaques, p-tau217 and tau tangles became positive at earlier ages and with less time between them than in neurotypical adults. The authors state this highlights the need for early therapeutic interventions in this population, though no treatment itself was tested.
Study details
- Study designlongitudinal study
- Participants198
- Evidence strengthModerate
Limitations
The comparison groups, while sizable for this specialized population (198 and 172 people), are still specific research cohorts, and the text available here describes only the amyloid-onset risk finding, not the full biomarker-cascade comparison referenced in the title.
How this study scored 56/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same 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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 198 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 | 1 / 7 | Cited 2 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 2 / 6 | Cited 1.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Fan Zhang: h-index 29 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41240365) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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