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Progressive worsening of adaptive functions in Down syndrome may be mediated by the complexing of soluble Abeta peptides with the alpha 7 nicotinic acetylcholine receptor: therapeutic implications
Deutsch SI, Rosse RB, Mastropaolo J, Chilton M.. Clinical neuropharmacology, 2003-09-01
Topic: Brain proteins, microglia and lab models
In persons with Down syndrome, soluble Abeta peptides, which result from the processing of the amyloid precursor protein, appear in the brain decades before the extracellular deposition of neuritic plaques. These soluble amyloidogenic peptides accumulate intraneuronally and can be secreted extracellularly. Their appearance has been reported in the brains of fetuses with Down syndrome. The extra gene dosage effect associated with trisomy 21 results in abnormalities of the processing of amyloid precursor protein in persons with Down syndrome. Abeta peptides, especially Abeta1-42, have been shown to form tight complexes with the alpha7 nicotinic acetylcholine receptor, interfering with transduction of the acetylcholine signal by this nicotinic receptor subtype. Furthermore, the selective binding of Abeta peptides by this nicotinic acetylcholine receptor subtype is associated with cytotoxicity. The alpha7 nicotinic acetylcholine receptor has unique electrophysiologic properties and plays a prominent role in normal psychophysiologic processes (eg, sensory inhibition) and cognition. In persons with Down syndrome there is a decrease in the ability to perform instrumental activities of daily living that worsen with aging. The progressive worsening of adaptive functions and cognition in persons with Down syndrome may be, at least in part, mediated by interference with this receptor by soluble Abeta peptides. In view of this complex formed by soluble Abeta peptides and the alpha7 nicotinic acetylcholine receptor, cholinergic interventions that have been developed for Alzheimer disease, including selective nicotinic ones, should be explored in Down syndrome. Ideally, selective cholinergic interventions would slow the progression of the worsening of adaptive function and emergence of dementia in persons with Down syndrome.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Deutsch, S. I., Rosse, R. B., Mastropaolo, J., & Chilton, M. (2003). Progressive worsening of adaptive functions in Down syndrome may be mediated by the complexing of soluble Abeta peptides with the alpha 7 nicotinic acetylcholine receptor: therapeutic implications. Clinical neuropharmacology. https://doi.org/10.1097/00002826-200309000-00013
Vancouver
Deutsch SI, Rosse RB, Mastropaolo J, Chilton M. Progressive worsening of adaptive functions in Down syndrome may be mediated by the complexing of soluble Abeta peptides with the alpha 7 nicotinic acetylcholine receptor: therapeutic implications. Clinical neuropharmacology. 2003. doi:10.1097/00002826-200309000-00013. PMID: 14520169.
BibTeX
@article{deutsch2003-14520169,
author = {Deutsch, S. I. and Rosse, R. B. and Mastropaolo, J. and Chilton, M.},
title = {{Progressive worsening of adaptive functions in Down syndrome may be mediated by the complexing of soluble Abeta peptides with the alpha 7 nicotinic acetylcholine receptor: therapeutic implications}},
journal = {Clinical neuropharmacology},
year = {2003},
doi = {10.1097/00002826-200309000-00013},
pmid = {14520169},
url = {https://doi.org/10.1097/00002826-200309000-00013}
}
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.
Key findings
- In persons with Down syndrome, soluble Abeta peptides, which result from the processing of the amyloid precursor protein, appear in the brain decades before the extracellular deposition of neuritic plaques.
- The extra gene dosage effect associated with trisomy 21 results in abnormalities of the processing of amyloid precursor protein in persons with Down syndrome.
- Furthermore, the selective binding of Abeta peptides by this nicotinic acetylcholine receptor subtype is associated with cytotoxicity.
Why it matters
This paper proposes that soluble Abeta peptides, especially Abeta1-42, form tight complexes with the alpha7 nicotinic acetylcholine receptor and may mediate progressive worsening of adaptive functions in Down syndrome. It is a hypothesis paper and does not show a treatment or cure.
Study details
- Evidence strengthLow
How this study scored 31/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 30 of the 96 points we could judge it on, which is 31 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Clinical neuropharmacology) |
| Journal's citation record | 1 / 4 | Clinical Neuropharmacology: journal h-index 106 (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 | 2003 — 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 17 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.7 citations a year over 25 year(s) since 2003 |
| Impact for its field and year | 1 / 6 | Cited 0.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Melissa Chilton holds only 4 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 1 / 3 | Veterans Health Administration: institution h-index 968 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 14520169) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 30 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 30 of the 96 points we could judge it on is 31 out of 100. |
| Total | 31 / 100 | — |
What each of these 20 components measures, and what this score is not →
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