Home › Research › Down syndrome and Alzheimer's
Trisomy 21 and the brain
Mrak RE, Griffin WS.. Journal of neuropathology and experimental neurology, 2004-07-01
Topic: Brain proteins, microglia and lab models
In fetuses with Down syndrome, neurons fail to show normal dendritic development, yielding a "tree in winter" appearance. This developmental failure is thought to result in mental retardation. In adults with Down syndrome, neuronal loss is dramatic and neurofibrillary and neuritic Abeta plaque pathologies are consistent with Alzheimer disease. These pathological changes are thought to underlie the neuropsychological and physiological changes in older individuals with Down syndrome. Two chromosome 21-based gene products, beta-amyloid precursor protein (betaAPP) and S100B, have been implicated in these neuronal and interstitial changes. Although not necessary for mental retardation and other features, betaAPP gene triplication is necessary, although perhaps not sufficient, for development of Alzheimer pathology. S100B is overexpressed throughout life in Down patients, and mice with extra copies of the S100B gene have dendritic abnormalities. S100B overexpression correlates with Alzheimer pathology in post-adolescent Down syndrome patients and has been implicated in Abeta plaque pathogenesis. Interleukin-1 (IL-1) is a non-chromosome-21-based cytokine that is also overexpressed throughout life in Down syndrome. IL-1 upregulates betaAPP and S100B expression and drives numerous neurodegenerative and self-amplifying cascades that support a neuroinflammatory component in the pathogenesis of sporadic and Down syndrome-related Alzheimer disease.
Key findings
- This developmental failure is thought to result in mental retardation.
Why it matters
This review discusses how beta-amyloid precursor protein and S100B, both from chromosome 21, are implicated in the neuronal and plaque changes in Down syndrome, with betaAPP gene triplication necessary but perhaps not sufficient for Alzheimer pathology. It is a mechanistic review and tests no treatment or prevention.
Study details
- Evidence strengthLow
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neuropathology and experimental neurology) |
| Journal's citation record | 2 / 4 | Journal of Neuropathology & Experimental Neurology: journal h-index 239 (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 | 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 | 1 / 5 | 2004 — older than 20 years, still counted |
| 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 | 5 / 7 | Cited 108 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.5 citations a year over 24 year(s) since 2004 |
| Impact for its field and year | 3 / 6 | Cited 6.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 other studies in this library |
| Still being cited | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author W. Sue T. Griffin: h-index 66 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | University of Arkansas for Medical Sciences: institution h-index 591 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15290893) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 40 / 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).
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. Check the citation against the original before you use it.
APA 7th
Mrak, R. E., & Griffin, W. S. (2004). Trisomy 21 and the brain. Journal of neuropathology and experimental neurology. https://doi.org/10.1093/jnen/63.7.679
Vancouver
Mrak RE, Griffin WS. Trisomy 21 and the brain. Journal of neuropathology and experimental neurology. 2004. doi:10.1093/jnen/63.7.679. PMID: 15290893.
BibTeX
@article{mrak2004-15290893,
author = {Mrak, R. E. and Griffin, W. S.},
title = {{Trisomy 21 and the brain}},
journal = {Journal of neuropathology and experimental neurology},
year = {2004},
doi = {10.1093/jnen/63.7.679},
pmid = {15290893},
url = {https://doi.org/10.1093/jnen/63.7.679}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 15.
Later studies that cite this one
9 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Down syndrome and Alzheimer's
Also tagged “down”
527 studies in the library carry the topic tag “down”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 527 tagged studies.