Association of tear fluid amyloid and tau levels with disease severity and neurodegeneration

Abstract

There has been increasing interest in finding non-invasive biomarkers for neurodegenerative diseases such as Alzheimer’s disease (AD). This observational study investigated AD-specific biomarkers in tear fluid. Tear fluid was collected from a total of 65 subjects, including 23 patients with subjective cognitive decline (SCD), 22 patients with mild cognitive impairment (MCI), 11 dementia patients and 9 healthy controls (HC). Levels of amyloid-beta peptides (AB38, AB40, AB42), total-tau (t-tau) and phosphorylated-tau (p-tau) were determined using multiplex immunoassays. Levels of AB40 and t-tau were detectable in the vast majority (> 94%) of tear fluid samples. Cerebrospinal fluid (CSF) was available from a subset of patients. In this group, tear t-tau levels were significantly higher in people with dementia compared to SCD patients. Tear t-tau levels were elevated in patients with neurodegeneration (classified according to the A/T/N system) compared to patients without neurodegeneration. Negative correlations were found between CSF AB42 and CSF t-tau, and between CSF AB42 and tear t-tau. In summary, this study shows the potential of tau proteins in tear fluid to be associated with disease severity and neurodegeneration.

Non-Invasive Nasal Discharge Fluid and Other Body Fluid Biomarkers in Alzheimer’s Disease

“…Gijs et al measured Aβ 42 in tears using multiplex immunoassays and found the Aβ 42 levels changed with increasing AD stage with an area under the curve (AUC) of 0.725 [ 118 ]. Other Aβ peptides, Aβ 38 and Aβ 40 , were also detected in their subsequent study [ 119 ]. Recently, Wang et al developed a biosensor and detected variable Aβ 42 levels in different age groups of healthy participants [ 120 ].…”

“…Recently, Wang et al developed a biosensor and detected variable Aβ 42 levels in different age groups of healthy participants [ 120 ]. Gijs et al also analyzed T-tau, and its levels were also able to discriminate between AD patients and healthy controls with an AUC of 0.81 [ 118 , 119 ]. Quantitative proteomic results profiled that lipocalin-1, dermcidin, lysozyme-C, and lacritin can serve AD biomarkers [ 121 ].…”

Alzheimer’s Disease Seen through the Eye: Ocular Alterations and Neurodegeneration

“…In this regard, a recent study also suggested the potential of t-tau and Aβ42 markers at the lacrimal level for the diagnosis/discrimination of AD [ 130 , 131 ] ( Table 1 ). The authors determined a gradual increase in both biomarkers in tears throughout cognitive decline [ 130 , 131 ]. Additionally, Kenny and colleagues observed that the total tear concentration of microRNA-200b-5p was highly upregulated in AD samples compared to the control group [ 132 ].…”

“…Both t-tau and p-tau showed no differential expression among the three patient groups [ 129 ]. Moreover, the association of tear amyloid and tau levels with AD severity and neurodegeneration was also studied, highlighting the potential of tau and Aβ proteins in tear fluid as markers of AD severity [ 130 , 131 ]. In this regard, a recent study also suggested the potential of t-tau and Aβ42 markers at the lacrimal level for the diagnosis/discrimination of AD [ 130 , 131 ] ( Table 1 ).…”

“…Moreover, the association of tear amyloid and tau levels with AD severity and neurodegeneration was also studied, highlighting the potential of tau and Aβ proteins in tear fluid as markers of AD severity [ 130 , 131 ]. In this regard, a recent study also suggested the potential of t-tau and Aβ42 markers at the lacrimal level for the diagnosis/discrimination of AD [ 130 , 131 ] ( Table 1 ). The authors determined a gradual increase in both biomarkers in tears throughout cognitive decline [ 130 , 131 ].…”