Tears a potential novel source of biomarkers for AD
A Spanish proof-of-concept study suggests that tears may be a useful novel source of biomarkers for Alzheimer’s disease (AD).
The most relevant identified protein was eukaryotic translation initiation factor 4E (eIF4E), which appeared in 55 percent of AD samples, but was absent in all control samples. Total microRNA abundance was found to be higher in tears from patients with AD. Among individual microRNAs, microRNA-200b-5p was identified as a potential biomarker for AD, with elevated levels present in AD tear fluid samples compared with controls. [Sci Rep 2019;9:15437]
During the early pathogenesis of AD, one of the few detectable changes is a transition from a cognitively normal state to mild cognitive impairment (MCI). “MCI is a high-risk state for the development of AD, but is a heterogeneous condition common among many neurodegenerative diseases as well as in unaffected individuals, with a large percentage of cases never converting to dementia, making this state very susceptible to misdiagnosis,” noted the researchers. [Acta Psychiatr Scand 2009;119:252-265]
Detection of early-stage AD is reliant on MRI, functional MRI and CT as well as protein biomarkers from cerebrospinal fluid, which present significant practical and/or financial challenges. [Cold Spring Harb Perspect Med 2012;2:a006213; Neuropsychologia 2008;46:1648-1656; Lancet Neurol 2006;5:228-234]
Tears represent a noninvasive biofluid but are largely unexplored as a biomarker source. “The lack of investigation into tear fluid is striking due to the numerous putative markers for AD based on eye changes in affected individuals, including pupillary size and response to light as well as plaque formation in the retina and lenses of AD patients,” remarked the researchers. [Front Neurosci 2016;10:536; Am J Alzheimers Dis Other Demen 2015;30:738-745]
The present study investigated possible differences in tear composition between healthy aged controls and cognitively impaired patients, and included 32 donors (36.4 percent male): nine patients with AD, eight individuals with MCI and 15 age-matched controls. The protein content and relative expression of microRNAs in their tear fluid were assessed by high-throughput proteomic and PCR-based platforms.
“We identified a panel of 12 proteins differentially expressed in the tear fluid of AD patients compared with controls,” wrote the researchers. Among these proteins was eIF4E, whose phosphorylated form was previously found to be elevated in brain tissue of AD patients. [Neuroreport 2004;15:2237-2240]
Quantitative analysis of microRNAs in tear samples revealed significantly higher concentrations of microRNA-sized molecules present within AD patients compared with control. “MicroRNA expression changes rapidly in response to cellular disruptions and is likely to be affected by the numerous degenerative processes associated with AD,” proposed the researchers. [Proc Natl Acad Sci USA 2007;104:1604-1609] MicroRNA-200b-5p was exclusively detected in AD samples, verifying it as a potential new biomarker.
“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 noninvasive and cost-effective diagnostic test for AD,” concluded the researchers.