Proteins and microRNAs are differentially expressed in tear fluid from patients with Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is characterized by a progressive loss of neurons and cognitive functions. Therefore, early diagnosis of AD is critical. The development of practical and non-invasive diagnostic tests for AD remains, however, an unmet need. In the present proof-of-concept study we investigated tear fluid as a novel source of disease-specific protein and microRNA-based biomarkers for AD development using samples from patients with mild cognitive impairment (MCI) and AD. Tear protein content was evaluated via liquid chromatography-mass spectrometry and microRNA content was profiled using a genome-wide high-throughput PCR-based platform. These complementary approaches identified enrichment of specific proteins and microRNAs in tear fluid of AD patients. In particular, we identified elongation initiation factor 4E (eIF4E) as a unique protein present only in AD samples. Total microRNA abundance was found to be higher in tears from AD patients. Among individual microRNAs, microRNA-200b-5p was identified as a potential biomarker for AD with elevated levels present in AD tear fluid samples compared to controls. Our study suggests that tears may be a useful novel source of biomarkers for AD and that the identification and verification of biomarkers within tears may allow for the development of a non-invasive and cost-effective diagnostic test for AD.

Body Fluid Biomarkers for Alzheimer’s Disease—An Up-To-Date Overview

“…Another study suggested the discriminatory power of tear T-tau and Aβ 42 , as their levels increased in AD patients [ 186 ]. Additionally, total microRNA abundance was also found at increased levels in AD patients, with microRNA-200b-5p as the most promising AD biomarker [ 183 , 187 ].…”

Protein Biomarkers for the Diagnosis of Alzheimer’s Disease at Different Stages of Neurodegeneration

“…Furthermore, the isolation of tears for the detection of possible AD biomarkers may provide an even less invasive approach. In this regard, a recent study has corroborated the presence of specific miRNAs in the tears of AD patients [ 49 ]. This finding is, therefore, a good starting for the search of potential AD markers in this fluid.…”

Detection of amyloid-beta and tau in tear fluid of patients with Alzheimer’s disease

“…Kallo et al (10) used mass spectrometry to compare ten priorly selected proteins in tear uid samples from AD patients versus controls and observed differences for lipocalin-1, lactotransferrin, extracellular glycoprotein lacritin, lysozyme-C, prolactin inducible protein and dermcidin. Kenny et al (11) used mass spectrometry on tear uid from AD patients versus controls. They identi ed a panel of 12 proteins that were differentially expressed in tear uid of AD patients compared to controls.…”

“…Kallo et al (10) identi ed differences in the total tear protein composition in AD patients. Recently, Kenny et al (11) performed differential expression of tear uid from AD patients and controls by mass spectrometry. Based on these studies, it is reasonable to assume presence of amyloid-beta and tau in tear uid.…”