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Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome
Tramutola A, Lanzillotta C, Barone E, Arena A, Zuliani I, Mosca L, Blarzino C, Butterfield DA et al.. Translational neurodegeneration, 2018-11-06
Topic: Brain proteins, microglia and lab models
Background Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways, including insulin signaling and autophagy, involved in pathology onset and progression. Within this context, the therapeutic use of mTOR-inhibitors may prevent/attenuate the neurodegenerative phenomena. By our work we aimed to rescue mTOR signalling in DS mice by a novel rapamycin intranasal administration protocol (InRapa) that maximizes brain delivery and reduce systemic side effects. Methods Ts65Dn mice were administered with InRapa for 12 weeks, starting at 6 months of age demonstrating, at the end of the treatment by radial arms maze and novel object recognition testing, rescued cognition. Results The analysis of mTOR signalling, after InRapa, demonstrated in Ts65Dn mice hippocampus the inhibition of mTOR (reduced to physiological levels), which led, through the rescue of autophagy and insulin signalling, to reduced APP levels, APP processing and APP metabolites production, as well as, to reduced tau hyperphosphorylation. In addition, a reduction of oxidative stress markers was also observed. Discussion These findings demonstrate that chronic InRapa administration is able to exert a neuroprotective effect on Ts65Dn hippocampus by reducing AD pathological hallmarks and by restoring protein homeostasis, thus ultimately resulting in improved cognition. Results are discussed in term of a potential novel targeted therapeutic approach to reduce cognitive decline and AD-like neuropathology in DS individuals.
Key findings
- Background Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles.
- Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD).
- Results The analysis of mTOR signalling, after InRapa, demonstrated in Ts65Dn mice hippocampus the inhibition of mTOR (reduced to physiological levels), which led, through the rescue of autophagy and insulin signalling, to reduced APP levels, APP processing and APP metabolites production, as well as, to reduced tau hyperphosphorylation.
- Discussion These findings demonstrate that chronic InRapa administration is able to exert a neuroprotective effect on Ts65Dn hippocampus by reducing AD pathological hallmarks and by restoring protein homeostasis, thus ultimately resulting in improved cognition.
- Results are discussed in term of a potential novel targeted therapeutic approach to reduce cognitive decline and AD-like neuropathology in DS individuals.
Why it matters
In a mouse model of Down syndrome, 12 weeks of intranasal rapamycin rescued cognition and reduced amyloid precursor protein levels, its processing, and tau hyperphosphorylation. These are animal results only, and the treatment has not been tested in people.
Study details
- Evidence strengthLow
How this study scored 47/100
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 (Translational neurodegeneration) |
| Journal's citation record | 1 / 4 | Translational Neurodegeneration: journal h-index 93 (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 | 2 / 5 | 2018 — within 10 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 | 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 | 5 / 7 | Cited 101 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.1 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 4 / 6 | Cited 8.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 2 / 4 | Cited 26 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 3 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30410750) |
| Free to read | 2 / 2 | Free to read |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s40035-018-0133-9
- PubMed: 30410750
- Original source →
- Free full text: Translational Neurodegeneration →
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
Tramutola, A., Lanzillotta, C., Barone, E., Arena, A., Zuliani, I., Mosca, L., et al. (2018). Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome. Translational neurodegeneration. https://doi.org/10.1186/s40035-018-0133-9
Vancouver
Tramutola A, Lanzillotta C, Barone E, Arena A, Zuliani I, Mosca L, et al. Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome. Translational neurodegeneration. 2018. doi:10.1186/s40035-018-0133-9. PMID: 30410750.
BibTeX
@article{tramutola2018-30410750,
author = {Tramutola, A. and Lanzillotta, C. and Barone, E. and Arena, A. and Zuliani, I. and Mosca, L. and Blarzino, C. and Butterfield, D. A. and others},
title = {{Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome}},
journal = {Translational neurodegeneration},
year = {2018},
doi = {10.1186/s40035-018-0133-9},
pmid = {30410750},
url = {https://doi.org/10.1186/s40035-018-0133-9}
}
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