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Neuropathological role of PI3K/Akt/mTOR axis in Down syndrome brain
Perluigi M, Pupo G, Tramutola A, Cini C, Coccia R, Barone E, Head E, Butterfield DA et al.. Biochimica et biophysica acta, 2014-04-13
Topic: Brain proteins, microglia and lab models
Down syndrome (DS) is the most frequent genetic cause of intellectual disability characterized by the presence of three copies of chromosome 21 (Chr21). Individuals with DS have sufficient neuropathology for a diagnosis of Alzheimer's disease (AD) after the age of 40years. The aim of our study is to gain new insights in the molecular mechanisms impaired in DS subjects that eventually lead to the development of dementia. We evaluate the PI3K/Akt/mTOR axis in the frontal cortex from DS cases (under the age of 40years) and DS with AD neuropathology compared with age-matched controls (Young and Old). The PI3K/Akt/mTOR axis may control several key pathways involved in AD that, if aberrantly regulated, affect amyloid beta (Aβ) deposition and tau phosphorylation. Our results show a hyperactivation of PI3K/Akt/mTOR axis in individuals with DS, with and without AD pathology, in comparison with respective controls. The PI3K/Akt/mTOR deregulation results in decreased autophagy, inhibition of IRS1 and GSK3β activity. Moreover, our data suggest that aberrant activation of the PI3K/Akt/mTOR axis acts in parallel to RCAN1 in phosphorylating tau, in DS and DS/AD. In conclusion, this study provides insights into the neuropathological mechanisms that may be engaged during the development of AD in DS. We suggest that deregulation of this signaling cascade is already evident in young DS cases and persist in the presence of AD pathology. The impairment of the PI3K/Akt/mTOR axis in DS population might represent a key-contributing factor to the neurodegenerative process that culminates in Alzheimer-like dementia.
Key findings
- We evaluate the PI3K/Akt/mTOR axis in the frontal cortex from DS cases (under the age of 40years) and DS with AD neuropathology compared with age-matched controls (Young and Old).
- Our results show a hyperactivation of PI3K/Akt/mTOR axis in individuals with DS, with and without AD pathology, in comparison with respective controls.
- The PI3K/Akt/mTOR deregulation results in decreased autophagy, inhibition of IRS1 and GSK3β activity.
- Moreover, our data suggest that aberrant activation of the PI3K/Akt/mTOR axis acts in parallel to RCAN1 in phosphorylating tau, in DS and DS/AD.
- In conclusion, this study provides insights into the neuropathological mechanisms that may be engaged during the development of AD in DS.
Why it matters
In frontal cortex tissue, this study found hyperactivation of the PI3K/Akt/mTOR axis in people with Down syndrome, with and without Alzheimer pathology, along with decreased autophagy and inhibition of IRS1 and GSK3β. It suggests a mechanism that may operate early in the development of Alzheimer disease in Down syndrome but tests no treatment.
Study details
- Evidence strengthLow
How this study scored 45/100
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. We have no data on journal's citation record, so that was left out: it earned 43 of the 96 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biochimica et biophysica acta) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2014 — within 20 year(s) of the newest study here |
| 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 155 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.1 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 4 / 6 | Cited 9.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 22 other studies in this library |
| Still being cited | 2 / 4 | Cited 25 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Fabio Di Domenico: h-index 57 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Sapienza University of Rome: institution h-index 1,145 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 24735980) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 43 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 43 of the 96 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.bbadis.2014.04.007
- PubMed: 24735980
- Original source →
- Free full text: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease →
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
Perluigi, M., Pupo, G., Tramutola, A., Cini, C., Coccia, R., Barone, E., et al. (2014). Neuropathological role of PI3K/Akt/mTOR axis in Down syndrome brain. Biochimica et biophysica acta. https://doi.org/10.1016/j.bbadis.2014.04.007
Vancouver
Perluigi M, Pupo G, Tramutola A, Cini C, Coccia R, Barone E, et al. Neuropathological role of PI3K/Akt/mTOR axis in Down syndrome brain. Biochimica et biophysica acta. 2014. doi:10.1016/j.bbadis.2014.04.007. PMID: 24735980.
BibTeX
@article{perluigi2014-24735980,
author = {Perluigi, M. and Pupo, G. and Tramutola, A. and Cini, C. and Coccia, R. and Barone, E. and Head, E. and Butterfield, D. A. and others},
title = {{Neuropathological role of PI3K/Akt/mTOR axis in Down syndrome brain}},
journal = {Biochimica et biophysica acta},
year = {2014},
doi = {10.1016/j.bbadis.2014.04.007},
pmid = {24735980},
url = {https://doi.org/10.1016/j.bbadis.2014.04.007}
}
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