Home › Research › TREM2 and immune genetics
Alzheimer's disease-linked risk alleles elevate microglial cGAS-associated senescence and neurodegeneration in a tauopathy model
Carling GK, Fan L, Foxe NR, Norman K, Wong MY, Zhu D, Corona C, Razzoli A et al.. Neuron, 2024-09-30
Topic: Amyloid, tau and blood-test diagnosis
The strongest risk factors for late-onset sporadic Alzheimer's disease (AD) include the ε4 allele of apolipoprotein E (APOE), the R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2), and female sex. Here, we combine APOE4 and TREM2 R47H (R47H) in female P301S tauopathy mice to identify the pathways activated when AD risk is the strongest, thereby highlighting detrimental disease mechanisms. We find that R47H induces neurodegeneration in 9- to 10-month-old female APOE4 tauopathy mice.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Carling, G. K., Fan, L., Foxe, N. R., Norman, K., Wong, M. Y., Zhu, D., et al. (2024). Alzheimer's disease-linked risk alleles elevate microglial cGAS-associated senescence and neurodegeneration in a tauopathy model. Neuron. https://doi.org/10.1016/j.neuron.2024.09.006
Vancouver
Carling GK, Fan L, Foxe NR, Norman K, Wong MY, Zhu D, et al. Alzheimer's disease-linked risk alleles elevate microglial cGAS-associated senescence and neurodegeneration in a tauopathy model. Neuron. 2024. doi:10.1016/j.neuron.2024.09.006. PMID: 39353433.
BibTeX
@article{carling2024-39353433,
author = {Carling, G. K. and Fan, L. and Foxe, N. R. and Norman, K. and Wong, M. Y. and Zhu, D. and Corona, C. and Razzoli, A. and others},
title = {{Alzheimer's disease-linked risk alleles elevate microglial cGAS-associated senescence and neurodegeneration in a tauopathy model}},
journal = {Neuron},
year = {2024},
doi = {10.1016/j.neuron.2024.09.006},
pmid = {39353433},
url = {https://doi.org/10.1016/j.neuron.2024.09.006}
}
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.
Key findings
- Here, we combine APOE4 and TREM2 R47H (R47H) in female P301S tauopathy mice to identify the pathways activated when AD risk is the strongest, thereby highlighting detrimental disease mechanisms.
- We find that R47H induces neurodegeneration in 9- to 10-month-old female APOE4 tauopathy mice.
- The combination of APOE4 and R47H (APOE4-R47H) worsened hyperphosphorylated tau pathology in the frontal cortex and amplified tauopathy-induced microglial cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling and downstream interferon response.
- APOE4-R47H microglia displayed cGAS- and BAX-dependent upregulation of senescence, showing association between neurotoxic signatures and implicating mitochondrial permeabilization in pathogenesis.
Why it matters
In female tauopathy mice carrying both APOE4 and the TREM2 R47H variant, the combination worsened tau pathology and microglial changes and caused neurodegeneration. This is animal research only and reports no treatment, cure or prevention for people.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 51/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuron) |
| Journal's citation record | 4 / 4 | Neuron: journal h-index 689 (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 | 4 / 5 | 2024 — within 3 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 | 4 / 7 | Cited 80 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 20.0 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 4 / 6 | Cited 19.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 3 / 4 | Cited 80 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Li Gan: h-index 71 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39353433) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 51 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 44.
Later studies that cite this one
2 studies in the alzhub library list this one in their references.
Related studies in TREM2 and immune genetics
Also tagged “precursor”
1,339 studies in the library carry the topic tag “precursor”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,339 tagged studies.