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Integrating neuroinflammation biomarkers into the ATN(X) framework: Advances in Alzheimer's pathogenesis, diagnosis, and insights from non-human primate models
Zhihui Jin, Yan Lu, Huifang Tang, Huashun Cui. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025-08
Topic: Inflammation, microglia and astrocytes
The amyloid/tau/neurodegeneration (ATN) biomarker framework has greatly progressed the diagnosis and staging of Alzheimer's disease (AD). However, recent research highlights neuroinflammation as an equally critical factor in AD pathology across humans, rodents, and non-human primates (NHPs). This review evaluates the combined use of ATN and neuroinflammatory biomarkers-such as glial fibrillary acidic protein (GFAP) (astrocytic marker) and triggering receptor expressed on myeloid cells 2 (TREM2)/ ionized calcium-binding adapter molecule 1 (IBA-1) (microglial markers)-in elucidating AD mechanisms, promoting early diagnosis, and shaping therapeutic strategies. It also summarizes the key features and translational potential of NHP models that closely mimic human AD pathology, highlighting the promising prospects of integrating these models with the ATN(X) biomarker system. These insights strengthen the link between biomarkers, NHP research, and clinical practice, opening new avenues for the early detection and treatment strategies of AD. HIGHLIGHTS: Neuroinflammation biomarkers, including glial fibrillary acidic protein (GFAP), triggering receptor expressed on myeloid cells 2 (TREM2)/sTREM2, and YKL-40, show strong clinical potential in Alzheimer's disease (AD). Incorporating neuroinflammation biomarkers into the ATN(X) framework may enhance diagnostic precision. Advanced non-human primate (NHP) models closely replicate human brain pathology, addressing key limitations of mouse models. Measuring ATN(X) biomarkers in NHPs may improve clinical translation and support early diagnosis of AD. Optimizing NHP models-including ApoE4 status, injection protocols, and gene-editing approaches-is crucial for reproducibility and efficiency.
Key findings
- HIGHLIGHTS: Neuroinflammation biomarkers, including glial fibrillary acidic protein (GFAP), triggering receptor expressed on myeloid cells 2 (TREM2)/sTREM2, and YKL-40, show strong clinical potential in Alzheimer's disease (AD).
- Incorporating neuroinflammation biomarkers into the ATN(X) framework may enhance diagnostic precision.
- Advanced non-human primate (NHP) models closely replicate human brain pathology, addressing key limitations of mouse models.
- Measuring ATN(X) biomarkers in NHPs may improve clinical translation and support early diagnosis of AD.
- Optimizing NHP models-including ApoE4 status, injection protocols, and gene-editing approaches-is crucial for reproducibility and efficiency.
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Study details
- Evidence strengthLow
How this study scored 46/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported and randomised / 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, multi-centre collaboration and free to read, so those were left out: it earned 26 of the 56 points we could judge it on, which is 46 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| 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 | Laboratory or animal study (title names “non-human primate”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40801241) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 26 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 26 of the 56 points we could judge it on is 46 out of 100. |
| Total | 46 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Jin, Z., Lu, Y., Tang, H., & Cui, H. (2025). Integrating neuroinflammation biomarkers into the ATN(X) framework: Advances in Alzheimer's pathogenesis, diagnosis, and insights from non-human primate models. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.70472
Vancouver
Jin Z, Lu Y, Tang H, Cui H. Integrating neuroinflammation biomarkers into the ATN(X) framework: Advances in Alzheimer's pathogenesis, diagnosis, and insights from non-human primate models. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. doi:10.1002/alz.70472. PMID: 40801241.
BibTeX
@article{jin2025-40801241,
author = {Jin, Zhihui and Lu, Yan and Tang, Huifang and Cui, Huashun},
title = {{Integrating neuroinflammation biomarkers into the ATN(X) framework: Advances in Alzheimer's pathogenesis, diagnosis, and insights from non-human primate models}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2025},
doi = {10.1002/alz.70472},
pmid = {40801241},
url = {https://doi.org/10.1002/alz.70472}
}
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