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Aberrant crosstalk between insulin signaling and mTOR in young Down syndrome individuals revealed by neuronal-derived extracellular vesicles
Perluigi M, Picca A, Montanari E, Calvani R, Marini F, Matassa R, Tramutola A, Villani A et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2021-11-23
Topic: Brain proteins, microglia and lab models
Introduction Intellectual disability, accelerated aging, and early-onset Alzheimer-like neurodegeneration are key brain pathological features of Down syndrome (DS). Although growing research aims at the identification of molecular pathways underlying the aging trajectory of DS population, data on infants and adolescents with DS are missing. Methods Neuronal-derived extracellular vesicles (nEVs) were isolated form healthy donors (HDs, n = 17) and DS children (n = 18) from 2 to 17 years of age and nEV content was interrogated for markers of insulin/mTOR pathways. Results nEVs isolated from DS children were characterized by a significant increase in pIRS1 Ser636 , a marker of insulin resistance, and the hyperactivation of the Akt/mTOR/p70S6K axis downstream from IRS1, likely driven by the higher inhibition of Phosphatase and tensin homolog (PTEN). High levels of pGSK3β Ser9 were also found. Conclusions The alteration of the insulin-signaling/mTOR pathways represents an early event in DS brain and likely contributes to the cerebral dysfunction and intellectual disability observed in this unique population.
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APA 7th
Perluigi, M., Picca, A., Montanari, E., Calvani, R., Marini, F., Matassa, R., et al. (2022). Aberrant crosstalk between insulin signaling and mTOR in young Down syndrome individuals revealed by neuronal-derived extracellular vesicles. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.12499
Vancouver
Perluigi M, Picca A, Montanari E, Calvani R, Marini F, Matassa R, et al. Aberrant crosstalk between insulin signaling and mTOR in young Down syndrome individuals revealed by neuronal-derived extracellular vesicles. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022. doi:10.1002/alz.12499. PMID: 34812584.
BibTeX
@article{perluigi2022-34812584,
author = {Perluigi, M. and Picca, A. and Montanari, E. and Calvani, R. and Marini, F. and Matassa, R. and Tramutola, A. and Villani, A. and others},
title = {{Aberrant crosstalk between insulin signaling and mTOR in young Down syndrome individuals revealed by neuronal-derived extracellular vesicles}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2022},
doi = {10.1002/alz.12499},
pmid = {34812584},
url = {https://doi.org/10.1002/alz.12499}
}
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Key findings
- Results nEVs isolated from DS children were characterized by a significant increase in pIRS1 Ser636 , a marker of insulin resistance, and the hyperactivation of the Akt/mTOR/p70S6K axis downstream from IRS1, likely driven by the higher inhibition of Phosphatase and tensin homolog (PTEN).
Why it matters
This study found signs of insulin resistance and activation of the mTOR pathway in neuronal-derived extracellular vesicles from children with Down syndrome. It suggests these changes occur early in the brain, but it does not test any treatment or prevention for Alzheimer disease.
Study details
- Participants17
- Evidence strengthLow
How this study scored 50/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 17 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 | 3 / 7 | Cited 34 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.7 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 3 / 6 | Cited 4.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 2 / 4 | Cited 18 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Eugenio Barone: h-index 47 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Sapienza University of Rome: institution h-index 1,145 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34812584) |
| Free to read | 2 / 2 | Free to read |
| Total | 50 / 100 | — |
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