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The potential and challenges of TREM2-targeted therapy in Alzheimer's disease: insights from the INVOKE-2 study
Ma YN, Hu X, Karako K, Song P, Tang W, Xia Y.. Frontiers in aging neuroscience, 2025-04-25
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Alzheimer's disease (AD) is a severe neurodegenerative disorder with a growing global burden. With the rising incidence of AD, the need for novel therapeutic targets has become increasingly critical. TREM2, a receptor expressed on microglial cells, plays a crucial role in modulating neuroinflammation and clearing pathological substrates, making it a promising candidate for AD therapy. However, the recent clinical trial INVOKE-2 failed to demonstrate significant clinical benefits of the TREM2-targeted antibody AL002, raising doubts about the efficacy of TREM2-targeted methods. This article examines the role of TREM2 in AD pathogenesis, evaluates potential reasons for the disappointing outcomes of the INVOKE-2 trial, and discusses future directions for TREM2-based therapies. Factors such as treatment timing, dosage optimization, patient genetic variability, and combination therapy strategies are identified as critical determinants of therapeutic success. Future studies should aim to refine treatment strategies, identify precise indications, and explore the potential for combination therapies to enhance efficacy.
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APA 7th
Ma, Y. N., Hu, X., Karako, K., Song, P., Tang, W., & Xia, Y. (2025). The potential and challenges of TREM2-targeted therapy in Alzheimer's disease: insights from the INVOKE-2 study. Frontiers in aging neuroscience. https://doi.org/10.3389/fnagi.2025.1576020
Vancouver
Ma YN, Hu X, Karako K, Song P, Tang W, Xia Y. The potential and challenges of TREM2-targeted therapy in Alzheimer's disease: insights from the INVOKE-2 study. Frontiers in aging neuroscience. 2025. doi:10.3389/fnagi.2025.1576020. PMID: 40353063.
BibTeX
@article{ma2025-40353063,
author = {Ma, Y. N. and Hu, X. and Karako, K. and Song, P. and Tang, W. and Xia, Y.},
title = {{The potential and challenges of TREM2-targeted therapy in Alzheimer's disease: insights from the INVOKE-2 study}},
journal = {Frontiers in aging neuroscience},
year = {2025},
doi = {10.3389/fnagi.2025.1576020},
pmid = {40353063},
url = {https://doi.org/10.3389/fnagi.2025.1576020}
}
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Key findings
- However, the recent clinical trial INVOKE-2 failed to demonstrate significant clinical benefits of the TREM2-targeted antibody AL002, raising doubts about the efficacy of TREM2-targeted methods.
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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 randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 26 of the 58 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in aging neuroscience) |
| 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 | 4 / 5 | 2025 — 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40353063) |
| Free to read | 2 / 2 | Free to read |
| Points | 26 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 26 of the 58 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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