Tear Biomarkers in Alzheimer’s and Parkinson’s Diseases, and Multiple Sclerosis: Implications for Diagnosis (Systematic Review)

Abstract

Biological material is one of the most important aspects that allow for the correct diagnosis of the disease, and tears are an interesting subject of research because of the simplicity of collection, as the well as the relation to the components similar to other body fluids. In this review, biomarkers for Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS) in tears are investigated and analyzed. Records were obtained from the PubMed and Google Scholar databases in a timeline of 2015–2022. The keywords were: tear film/tear biochemistry/tear biomarkers + diseases (AD, PD, or MS). The recent original studies were analyzed, discussed, and biomarkers present in tears that can be used for the diagnosis and management of AD, PD, and MS diseases were shown. α-synTotal and α-synOligo, lactoferrin, norepinephrine, adrenaline, epinephrine, dopamine, α-2-macroglobulin, proteins involved in immune response, lipid metabolism and oxidative stress, apolipoprotein superfamily, and others were shown to be biomarkers in PD. For AD as potential biomarkers, there are: lipocalin-1, lysozyme-C, and lacritin, amyloid proteins, t-Tau, p-Tau; for MS there are: oligoclonal bands, lipids containing choline, free carnitine, acylcarnitines, and some amino acids. Information systematized in this review provides interesting data and new insight to help improve clinical outcomes for patients with neurodegenerative disorders.

The Eye as a Diagnostic Tool for Alzheimer’s Disease

“…Moreover, tear fluid, in contrast to CSF and blood, currently requires sample preprocessing that involves dilution, further reducing protein concentration [ 115 ]. Overall, due to the simple sample collection methods and availability, tear analysis appears to be a worthwhile target of further investigation as a screening tool for AD [ 118 ].…”

Smart Contact Lenses as Wearable Ophthalmic Devices for Disease Monitoring and Health Management

“…The authors presumed that this is due to the larger contribution of the lacrimal gland to reflex tears than basal tears, resulting in a larger difference in the composition of reflex tears from the healthy controls. The other study investigated the content of the oligomeric α-Syn in tears depending on the stage of the PD . In comparison with healthy control tears, the oligomeric α-Syn increased by 8.6-fold (4.43 ± 1.26 ng mg –1 tear protein), 4.5-fold (2.3 ± 0.54 ng mg –1 tear protein), 3.7-fold (1.9 ± 0.59 ng mg –1 tear protein) in tears of the early, intermediate, and late stage of PD, respectively.…”

“…Neurodegenerative diseases bring about a dysfunction of the lacrimal gland since it is innervated by parasympathetic and sympathetic neurons. 213 The degeneration of these neurons can alter the secretion or the composition of tears. These alterations contribute to discrimination of tear composition from the patients and the healthy controls, leading to identification of biomarkers of neurodegenerative diseases.…”

“…The other study investigated the content of the oligomeric α-Syn in tears depending on the stage of the PD. 213 In comparison with healthy control tears, the oligomeric α-Syn increased by 8.6-fold (4.43 ± 1.26 ng mg −1 tear protein), 4.5-fold (2.3 ± 0.54 ng mg −1 tear protein), 3.7fold (1.9 ± 0.59 ng mg −1 tear protein) in tears of the early, intermediate, and late stage of PD, respectively. In addition to α-Syn, CCL2 and DJ-1 are potential biomarkers in tears for PD.…”

Tear exosomes: A messenger of clinical health complication

“…The presence of proteins in tears that are also present in cerebrospinal fluid enhances their potential for non-invasive early detection of neurological disorders and offers valuable insights into one's overall physical well-being. 1 Recent studies indicate a gradual but significant advancement in understanding the interplay of autophagy and exosome pathogenesis in ocular diseases such as dry eye disease, corneal allograft rejection, corneal injury, keratitis, corneal dystrophy and keratoconus. Notably, this research emphasizes the potential utility of tear exosomes for detecting ocular diseases.…”