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Neuroinflammatory fluid biomarkers in patients with Alzheimer's disease: a systematic literature review
Heneka MT, Gauthier S, Chandekar SA, Hviid Hahn-Pedersen J, Bentsen MA, Zetterberg H.. Molecular psychiatry, 2025-03-06
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Introduction Neuroinflammation is associated with both early and late stages of the pathophysiology of Alzheimer's disease (AD). Fluid biomarkers are gaining significance in clinical practice for diagnosis in presymptomatic stages, monitoring, and disease prognosis. This systematic literature review (SLR) aimed to identify fluid biomarkers for neuroinflammation related to clinical stages across the AD continuum and examined long-term outcomes associated with changes in biomarkers. Methods The SLR was conducted per the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We used PubMed®, Embase®, and Cochrane Collaboration databases to search for articles in English (between 2012 and 2022) on AD or mild cognitive impairment due to AD, using "neuroinflammation" or other "immune" search strings. Two independent reviewers screened titles and examined data from full-text articles for the SLR. Results After the initial screening, 54 studies were prioritized for data extraction based upon their relevance to the SLR research questions. Nine studies for YKL-40, seven studies for sTREM2, and 11 studies for GFAP examined the relationship between the neuroinflammatory biomarkers and the clinical stage of the disease. Nine longitudinal studies further explored the association of fluid biomarkers with long-term clinical outcomes of disease. Cerebrospinal fluid (CSF) levels of YKL-40 were elevated in patients with AD dementia, while CSF sTREM2 levels were more strongly associated with preclinical and early symptomatic stages of AD. Plasma GFAP levels remained consistently elevated both in patients with AD dementia and individuals in preclinical stages with β-amyloid pathology. Longitudinal changes in plasma GFAP appeared to be predictive of cognitive decline in patients over time. Discussion Neuroinflammatory biomarkers are associated with AD progression. More longitudinal studies in the preclinical and MCI stages of AD are needed to validate fluid biomarkers for diagnosis, disease monitoring, and prognosis in clinical practice.
What this study adds
Evidence grade: High
This is a pooled review. Changes in blood GFAP over time appeared to predict cognitive decline. The authors say more long-term studies are needed before these markers are used routinely for diagnosis and monitoring.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Heneka, M. T., Gauthier, S., Chandekar, S. A., Hviid Hahn-Pedersen, J., Bentsen, M. A., & Zetterberg, H. (2025). Neuroinflammatory fluid biomarkers in patients with Alzheimer's disease: a systematic literature review. Molecular psychiatry. https://doi.org/10.1038/s41380-025-02939-9
Vancouver
Heneka MT, Gauthier S, Chandekar SA, Hviid Hahn-Pedersen J, Bentsen MA, Zetterberg H. Neuroinflammatory fluid biomarkers in patients with Alzheimer's disease: a systematic literature review. Molecular psychiatry. 2025. doi:10.1038/s41380-025-02939-9. PMID: 40050444.
BibTeX
@article{heneka2025-40050444,
author = {Heneka, M. T. and Gauthier, S. and Chandekar, S. A. and Hviid Hahn-Pedersen, J. and Bentsen, M. A. and Zetterberg, H.},
title = {{Neuroinflammatory fluid biomarkers in patients with Alzheimer's disease: a systematic literature review}},
journal = {Molecular psychiatry},
year = {2025},
doi = {10.1038/s41380-025-02939-9},
pmid = {40050444},
url = {https://doi.org/10.1038/s41380-025-02939-9}
}
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
- Introduction Neuroinflammation is associated with both early and late stages of the pathophysiology of Alzheimer's disease (AD).
- This systematic literature review (SLR) aimed to identify fluid biomarkers for neuroinflammation related to clinical stages across the AD continuum and examined long-term outcomes associated with changes in biomarkers.
- Results After the initial screening, 54 studies were prioritized for data extraction based upon their relevance to the SLR research questions.
- Cerebrospinal fluid (CSF) levels of YKL-40 were elevated in patients with AD dementia, while CSF sTREM2 levels were more strongly associated with preclinical and early symptomatic stages of AD.
- Discussion Neuroinflammatory biomarkers are associated with AD progression.
Why it matters
Reviewing 54 studies, the authors found that inflammation markers in body fluids track different stages of Alzheimer's: spinal fluid YKL-40 was raised in Alzheimer's dementia, sTREM2 was more tied to early stages, and blood GFAP was raised both in dementia and in people with amyloid but no symptoms. Changes in blood GFAP over time appeared to predict cognitive decline. The authors say more long-term studies are needed before these markers are used routinely for diagnosis and monitoring.
Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 72/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | 3 / 4 | Molecular Psychiatry: journal h-index 318 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” 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 | A review of other studies — randomization is not credited here |
| Times cited | 4 / 7 | Cited 70 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 23.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 16.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 3 / 4 | Cited 70 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Henrik Zetterberg: h-index 196 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 12 institution(s) in 6 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40050444) |
| Free to read | 2 / 2 | Free to read |
| Total | 72 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41380-025-02939-9
- PubMed: 40050444
- Original source →
- Free full text: Molecular Psychiatry →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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