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Microglial mTOR Activation Upregulates Trem2 and Enhances β-Amyloid Plaque Clearance in the 5XFAD Alzheimer's Disease Model
Shi Q, Chang C, Saliba A, Bhat MA.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2022-06-07
Topic: Brain proteins, microglia and lab models
The mechanistic target of rapamycin (mTOR) signaling pathway plays a major role in key cellular processes including metabolism and differentiation; however, the role of mTOR in microglia and its importance in Alzheimer's disease (AD) have remained largely uncharacterized. We report that selective loss of Tsc1 , a negative regulator of mTOR, in microglia in mice of both sexes, caused mTOR activation and upregulation of Trem2 with enhanced β-Amyloid (Aβ) clearance, reduced spine loss, and improved cognitive function in the 5XFAD AD mouse model. Combined loss of Tsc1 and Trem2 in microglia led to reduced Aβ clearance and increased Aβ plaque burden revealing that Trem2 functions downstream of mTOR.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Shi, Q., Chang, C., Saliba, A., & Bhat, M. A. (2022). Microglial mTOR Activation Upregulates Trem2 and Enhances β-Amyloid Plaque Clearance in the 5XFAD Alzheimer's Disease Model. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.2427-21.2022
Vancouver
Shi Q, Chang C, Saliba A, Bhat MA. Microglial mTOR Activation Upregulates Trem2 and Enhances β-Amyloid Plaque Clearance in the 5XFAD Alzheimer's Disease Model. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2022. doi:10.1523/jneurosci.2427-21.2022. PMID: 35672148.
BibTeX
@article{shi2022-35672148,
author = {Shi, Q. and Chang, C. and Saliba, A. and Bhat, M. A.},
title = {{Microglial mTOR Activation Upregulates Trem2 and Enhances β-Amyloid Plaque Clearance in the 5XFAD Alzheimer's Disease Model}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2022},
doi = {10.1523/jneurosci.2427-21.2022},
pmid = {35672148},
url = {https://doi.org/10.1523/jneurosci.2427-21.2022}
}
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
- We report that selective loss of Tsc1 , a negative regulator of mTOR, in microglia in mice of both sexes, caused mTOR activation and upregulation of Trem2 with enhanced β-Amyloid (Aβ) clearance, reduced spine loss, and improved cognitive function in the 5XFAD AD mouse model.
- Combined loss of Tsc1 and Trem2 in microglia led to reduced Aβ clearance and increased Aβ plaque burden revealing that Trem2 functions downstream of mTOR.
- Tsc1 mutant microglia showed increased phagocytosis with upregulation of CD68 and Lamp1 lysosomal proteins.
- In vitro studies using Tsc1 -deficient microglia revealed enhanced endocytosis of the lysosomal tracker indicator Green DND-26 suggesting increased lysosomal activity.
Why it matters
In the 5XFAD mouse model, activating mTOR in microglia upregulated Trem2 and enhanced amyloid-β clearance, reduced spine loss and improved cognitive function, with Trem2 acting downstream of mTOR. This is mouse work identifying a pathway and does not demonstrate a treatment for people.
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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 (The Journal of neuroscience : the official journal of the Society for Neuroscience) |
| Journal's citation record | 4 / 4 | Journal of Neuroscience: journal h-index 651 (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 | 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 “5xfad”) — 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 127 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 21.2 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 3 / 6 | Cited 7.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 3 / 4 | Cited 98 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Manzoor A. Bhat: h-index 38 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | The University of Texas at San Antonio Health Science Center: institution h-index 883 (OpenAlex) |
| Multi-centre 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 35672148) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1523/jneurosci.2427-21.2022
- PubMed: 35672148
- Original source →
- Free full text: PubMed Central →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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