Altered tear fluid protein expression in persons with mild cognitive impairment

Abstract

Background: 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). Objective: This study aimed to determine alterations in the expression of proteins in TF collected from persons with MCI compared with cognitively healthy controls. Methods: 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. Results: 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). Conclusions: 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.