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Neuroinflammation Markers in Tear Fluid of Mild Alzheimer’s Disease
Virve Kärkkäinen, Toni Tapani Saari, Minna Rusanen, Hannu M. T. Uusitalo, Ville Leinonen, Bernd Thiede, Kai Kaarniranta, Anne Maria Koivisto et al.. Journal of Molecular Neuroscience, 2025-06-05
Topic: Amyloid, tau and blood-test diagnosis
The protein composition of tear fluid (TF) reflects the severity and progression of many age-related diseases. Here, we evaluated TF proteins from patients with mild Alzheimer's disease (AD) and cognitively healthy controls (CO) to explore potential new biomarker molecules. The aim of this study was to explore potential new biomarker molecules by examining the expression of TF proteins whose function is related to neuroinflammation. We examined 53 participants (34 COs, mean age 71 years, Mini-Mental State Examination (MMSE) score 28.9 ± 1.4; 19 with AD, Clinical Dementia Rating 0.5-1, mean age 72 years, MMSE 23.8 ± 2.8). All participants underwent neurological status examination, cognitive testing, and ophthalmological examination. TF was collected using Schirmer strips, and TF protein content was evaluated using mass spectrometry-based proteomics and label-free quantification. We report 14 TF proteins that showed altered protein expression in the AD group compared to the CO group. Twelve proteins were significantly upregulated (SERPINA3, FGA, SIAS, ORM1, ANXA3, G6PI/NLK, CH3L2, MSLN, CPPED1, JCHAIN, IGHV5-51, SPARCL1) and two were downregulated (PIP, SCGB2A1) (p ≤ 0.05). Observed altered expression of TF proteins in the AD group may have potential in AD pathology. Since inflammation is one of the earliest signs of neurodegeneration in AD, these proteins are putative new biomarker candidates of early AD.
Key findings
- We report 14 TF proteins that showed altered protein expression in the AD group compared to the CO group.
- Twelve proteins were significantly upregulated (SERPINA3, FGA, SIAS, ORM1, ANXA3, G6PI/NLK, CH3L2, MSLN, CPPED1, JCHAIN, IGHV5-51, SPARCL1) and two were downregulated (PIP, SCGB2A1) (p ≤ 0.05).
Why it matters
In a small study of 53 people, 14 proteins related to neuroinflammation showed altered levels in tear fluid from those with mild Alzheimer's disease compared with healthy controls. This is biomarker research only and does not show that measuring these proteins can treat, cure or prevent the disease.
Study details
- Participants53
- Evidence strengthLow
How this study scored 42/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Molecular Neuroscience) |
| Journal's citation record | 1 / 4 | Journal of Molecular Neuroscience: journal h-index 118 (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 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 53 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 4 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Tor Paaske Utheim: h-index 48 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Helsinki: institution h-index 1,201 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 12 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40471493) |
| Free to read | 2 / 2 | Free to read |
| Total | 42 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1007/s12031-025-02368-x
- PubMed: 40471493
- Original source →
- Free full text: Journal of Molecular Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Kärkkäinen, V., Saari, T. T., Rusanen, M., Uusitalo, H. M. T., Leinonen, V., Thiede, B., et al. (2025). Neuroinflammation Markers in Tear Fluid of Mild Alzheimer’s Disease. Journal of Molecular Neuroscience. https://doi.org/10.1007/s12031-025-02368-x
Vancouver
Kärkkäinen V, Saari TT, Rusanen M, Uusitalo HMT, Leinonen V, Thiede B, et al. Neuroinflammation Markers in Tear Fluid of Mild Alzheimer’s Disease. Journal of Molecular Neuroscience. 2025. doi:10.1007/s12031-025-02368-x. PMID: 40471493.
BibTeX
@article{karkkainen2025-40471493,
author = {Kärkkäinen, Virve and Saari, Toni Tapani and Rusanen, Minna and Uusitalo, Hannu M. T. and Leinonen, Ville and Thiede, Bernd and Kaarniranta, Kai and Koivisto, Anne Maria and others},
title = {{Neuroinflammation Markers in Tear Fluid of Mild Alzheimer’s Disease}},
journal = {Journal of Molecular Neuroscience},
year = {2025},
doi = {10.1007/s12031-025-02368-x},
pmid = {40471493},
url = {https://doi.org/10.1007/s12031-025-02368-x}
}
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