# Altered tear fluid protein expression in persons with mild cognitive impairment

**Authors:** Virve Kärkkäinen, Toni Saari, Minna Rusanen, Hannu Uusitalo, Ville Leinonen, Bernd Thiede, Anne M. Koivisto, Kai Kaarniranta, Tor P. Utheim

PMC · DOI: 10.1177/13872877251413291 · 2026-01-20

## TL;DR

This study found changes in tear fluid proteins in people with mild cognitive impairment, suggesting tears could help detect early signs of memory disorders.

## Contribution

The study identifies altered tear fluid proteins in mild cognitive impairment, offering new potential biomarkers for early diagnosis of neurodegenerative diseases.

## Key findings

- 33 tear fluid proteins related to oxidative stress, clearance, cytoskeleton, and inflammation were altered in MCI patients.
- Altered proteins suggest cellular stress and may indicate increased risk for Alzheimer's or memory disorders.
- Tear fluid shows promise as a non-invasive source for early diagnostic biomarkers in neurodegenerative diseases.

## Abstract

Tear fluid (TF) is a protein-rich fluid reported to reflect pathophysiological changes in several neurodegenerative diseases, including Alzheimer's disease. TF proteins are increasingly being considered as putative biomarker candidates to help in the diagnosis of disease. However, little information is available on TF protein changes in persons with mild cognitive impairment (MCI).

This study aimed to determine alterations in the expression of proteins in TF collected from persons with MCI compared with cognitively healthy controls.

We analyzed data from 54 study participants, including 34 controls (mean age, 71 years; mean Mini-Mental State Examination [MMSE] score ± standard deviation, 28.9 ± 1.4) and 20 persons with MCI (mean age, 71 years; mean MMSE score, 27.1 ± 1.9). All participants underwent cognitive, neurological, and ophthalmological examinations. TF was collected using Schirmer strips and evaluated using mass spectrometry-based proteomics and label-free quantification.

The expression of 33 TF proteins involved in oxidative stress, clearance mechanism, cytoskeleton stability, and inflammation were altered in persons with MCI compared with controls (p ≤ 0.05).

Our findings reveal that numerous cellular stress-related biomarker candidate proteins are upregulated or downregulated in the TF of persons with MCI, a condition that may increase the risk of developing AD or other memory disorder. These data encourage TF protein studies in neurodegenerative diseases and TF provides an additive source of biomarkers for early diagnostics of memory diseases.

## Linked entities

- **Diseases:** Alzheimer's disease (MONDO:0004975)

## Full-text entities

- **Genes:** F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}
- **Diseases:** MCI (MESH:D060825), inflammation (MESH:D007249), cognitive impairment (MESH:D003072), AD (MESH:D000544), memory diseases (MESH:D008569), neurodegenerative diseases (MESH:D019636)

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12960749/full.md

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Source: https://tomesphere.com/paper/PMC12960749