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Mouse model of neurodegeneration: atrophy of basal forebrain cholinergic neurons in trisomy 16 transplants
Holtzman DM, Li YW, DeArmond SJ, McKinley MP, Gage FH, Epstein CJ, Mobley WC.. Proceedings of the National Academy of Sciences of the United States of America, 1992-02-01
Topic: Brain proteins, microglia and lab models
Plain-language summary
Vulnerability of specific brain regions and neuronal populations is a characteristic feature of Alzheimer disease and Down syndrome. Cholinergic neurons of the basal forebrain degenerate in both disorders. The basis for neuronal degeneration is unknown. Mouse trisomy 16 (Ts 16) is an animal model of Down syndrome. We sought an experimental system in which the survival and development of Ts 16 basal forebrain cholinergic neurons could be examined beyond the fetal period. As Ts 16 mice do not survive birth, we transplanted fetal Ts 16 and control basal forebrain into the hippocampus of young adult mice. Transplanted neurons survived and grew neurites in all grafts. Over time, we observed selective atrophy of cholinergic neurons in Ts 16 grafts. Denervation of the hippocampus produced a significant increase in the size of Ts 16 cholinergic neurons. This suggests that hippocampal-derived neurotrophic factors acted to prevent degeneration. beta/A4-amyloid-containing plaques were not seen. Ts 16 provides a model of spontaneous, genetically determined neurodegeneration that may be used to understand better the molecular pathogenesis of neuronal dysfunction in Alzheimer disease and Down syndrome.
What this study adds
Evidence grade: Low
This study used transplanted fetal brain tissue from trisomy 16 mice, a model of Down syndrome, and found that cholinergic neurons shrank over time. It suggests that hippocampal neurotrophic factors may prevent degeneration, but it is an animal study and does not test a treatment in humans.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Holtzman, D. M., Li, Y. W., DeArmond, S. J., McKinley, M. P., Gage, F. H., Epstein, C. J., et al. (1992). Mouse model of neurodegeneration: atrophy of basal forebrain cholinergic neurons in trisomy 16 transplants. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.89.4.1383
Vancouver
Holtzman DM, Li YW, DeArmond SJ, McKinley MP, Gage FH, Epstein CJ, et al. Mouse model of neurodegeneration: atrophy of basal forebrain cholinergic neurons in trisomy 16 transplants. Proceedings of the National Academy of Sciences of the United States of America. 1992. doi:10.1073/pnas.89.4.1383. PMID: 1741393.
BibTeX
@article{holtzman1992-1741393,
author = {Holtzman, D. M. and Li, Y. W. and DeArmond, S. J. and McKinley, M. P. and Gage, F. H. and Epstein, C. J. and Mobley, W. C.},
title = {{Mouse model of neurodegeneration: atrophy of basal forebrain cholinergic neurons in trisomy 16 transplants}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {1992},
doi = {10.1073/pnas.89.4.1383},
pmid = {1741393},
url = {https://doi.org/10.1073/pnas.89.4.1383}
}
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Over time, we observed selective atrophy of cholinergic neurons in Ts 16 grafts.
- Denervation of the hippocampus produced a significant increase in the size of Ts 16 cholinergic neurons.
- This suggests that hippocampal-derived neurotrophic factors acted to prevent degeneration. beta/A4-amyloid-containing plaques were not seen.
Why it matters
This study used transplanted fetal brain tissue from trisomy 16 mice, a model of Down syndrome, and found that cholinergic neurons shrank over time. It suggests that hippocampal neurotrophic factors may prevent degeneration, but it is an animal study and does not test a treatment in humans.
Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomized / 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 | 1992 — 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 |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 55 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.5 citations a year over 36 year(s) since 1992 |
| Impact for its field and year | 3 / 6 | Cited 6.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 0 / 4 | Cited 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author WC Mobley: h-index 11 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multicenter collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 1741393) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 38 / 100 | — |
What each of these 20 components measures, and what this score is not →
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