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Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome
Holtzman DM, Santucci D, Kilbridge J, Chua-Couzens J, Fontana DJ, Daniels SE, Johnson RM, Chen K et al.. Proceedings of the National Academy of Sciences of the United States of America, 1996-11-01
Topic: Brain proteins, microglia and lab models
To study the pathogenesis of central nervous system abnormalities in Down syndrome (DS), we have analyzed a new genetic model of DS, the partial trisomy 16 (Ts65Dn) mouse. Ts65Dn mice have an extra copy of the distal aspect of mouse chromosome 16, a segment homologous to human chromosome 21 that contains much of the genetic material responsible for the DS phenotype. Ts65Dn mice show developmental delay during the postnatal period as well as abnormal behaviors in both young and adult animals that may be analogous to mental retardation. Though the Ts65Dn brain is normal on gross examination, there is age-related degeneration of septohippocampal cholinergic neurons and astrocytic hypertrophy, markers of the Alzheimer disease pathology that is present in elderly DS individuals. These findings suggest that Ts65Dn mice may be used to study certain developmental and degenerative abnormalities in the DS brain.
Key findings
- These findings suggest that Ts65Dn mice may be used to study certain developmental and degenerative abnormalities in the DS brain.
Why it matters
This study describes a mouse model of Down syndrome that shows age-related loss of certain brain cells and other changes resembling Alzheimer's disease pathology. These are findings in mice, so they cannot yet be directly applied to treating or preventing Alzheimer's in people.
Study details
- Evidence strengthLow
How this study scored 49/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | 4 / 4 | Proceedings of the National Academy of Sciences: journal h-index 1,167 (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 | 1996 — 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 | Laboratory or animal study (title names “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 451 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.1 citations a year over 32 year(s) since 1996 |
| Impact for its field and year | 4 / 6 | Cited 12.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 16 other studies in this library |
| Still being cited | 2 / 4 | Cited 28 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author William Cary Mobley: h-index 84 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 8917591) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 49 / 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. 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
Holtzman, D. M., Santucci, D., Kilbridge, J., Chua-Couzens, J., Fontana, D. J., Daniels, S. E., et al. (1996). Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.93.23.13333
Vancouver
Holtzman DM, Santucci D, Kilbridge J, Chua-Couzens J, Fontana DJ, Daniels SE, et al. Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome. Proceedings of the National Academy of Sciences of the United States of America. 1996. doi:10.1073/pnas.93.23.13333. PMID: 8917591.
BibTeX
@article{holtzman1996-8917591,
author = {Holtzman, D. M. and Santucci, D. and Kilbridge, J. and Chua-Couzens, J. and Fontana, D. J. and Daniels, S. E. and Johnson, R. M. and Chen, K. and others},
title = {{Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {1996},
doi = {10.1073/pnas.93.23.13333},
pmid = {8917591},
url = {https://doi.org/10.1073/pnas.93.23.13333}
}
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Referenced by this study and also in the alzhub library, so you can read them here.
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