Elevated t-tau level in tears may signal neurodegeneration

Concentrations of tau protein seem to be higher in the tear fluids of neurodegenerative individuals, suggesting a potential role for the biomarker in the detection of cognitive impairment, a recent study has found.

Researchers enrolled 23 patients with subjective cognitive decline (SCD), 22 with mild cognitive impairment (MCI), and 11 with dementia. Multiplex immunoassays were used to measure levels of amyloid-beta (AB38, AB40, and AB42), total-tau (t-tau), and phosphorylated-tau (p-tau) in participants’ tear fluid. A parallel group of nine healthy controls was also included.

More than 94 percent of samples showed detectable levels of t-tau and AB40; meanwhile, AB38, AB42, and p-tau concentrations were detectable in >23 percent of specimens. Notably, AB42 was more distinctly detectable in healthy controls than all patient subgroups (78 percent vs <18 percent), while p-tau was almost completely absent in tears from healthy controls.

Across all diagnostic groups, the researchers found tear fluid levels of AB38, AB40, AB42, and t-tau to be nominally elevated relative to healthy controls; no such pattern was reported for p-tau.

Notably, when focusing on a subset of patients with available cerebrospinal fluid (CSF) biomarker measurements, t-tau was found to be elevated in both the CSF and tear fluid samples of participants with dementia and MCI relative to SCD. Moreover, median tear fluid t-tau levels were significantly elevated in patients with vs without neurodegeneration (4.30 vs 2.54; p=0.04).

“Unfortunately, tear fluid, in contrast to CSF and blood, requires sample preprocessing that involves dilution of the original sample volume. Moreover, ultrasensitive immunoassays often require large sample volumes,” the researchers said. “Working with biological samples with limited sample volumes such as tear fluid is therefore challenging.”