Korean medical researchers have discovered a biomarker to detect Alzheimer's disease in tears.
A research team -- led by Professor Ji Yong-woo of the Department of Ophthalmology at Yongin Severance Hospital and Professor Haam Seung-joo of the Department of Chemical and Biomedical Engineering at Yonsei University – said Tuesday it has developed an immunoassay for early diagnosis of Alzheimer's disease and used it to discover biomarkers in tears.
The eyes are connected to the brain and are used to identify Alzheimer's disease.
Diagnosis using tears is gaining attention because it does not require complex preparation, is inexpensive, and is directly linked to the central nervous system, which directly reflects the effects of cranial nervous system (CNS) diseases.
The research team aimed to develop a new framework for the early diagnosis of Alzheimer’s disease by discovering biomarkers based on tear samples of AD patients and developing a low-cost, high-sensitivity sensing platform.
The research largely consisted of two main processes. First, they conducted proteomic identification analysis using high-resolution mass spectrometry to explore and select biomarker candidates in a representative group of patients. Then, they developed a sensing platform to detect validated biomarkers with high sensitivity and validate them in tear samples.
The sensing platform developed by the team utilizes self-assembled nanoparticle-mediated amplified fluorogenic immunoassay (SNAFIA) that can selectively detect only selected candidates. These immunoassays are functionalized for immediate application in discovering new biomarkers by emitting amplified fluorescent signals through antigen-antibody reactions, which can be applied to the diagnosis of various diseases and are effective for early diagnosis of diseases.
The study's results confirmed that CAP1 protein, a biomarker candidate detected in a representative group of patients, is a valid biomarker for Alzheimer's disease. SNAFIA analysis of tear samples showed a progressive increase in fluorescence signal values, indicating the presence of CAP1 protein with disease progression.
In the mild cognitive impairment and AD groups, the area under the curve (AUC) values were 0.762 and 0.971, which were significant compared to the normal group. The researchers also found a significant correlation between the results of the MMSE and the sensing platform analysis, suggesting the validity of non-invasive diagnosis of AD using the sensing platform and tears.
"Simple and accurate fluid-based non-invasive measurement technologies, such as SNAFIA, will improve the painful and expensive nature of existing Alzheimer's disease tests and become an effective tool for early diagnosis," Professor Ji said. "In the future, integrating our SNAFIA platform into ophthalmic medical devices, including contact and intraocular lenses, could provide real-time monitoring of Alzheimer's disease."
The findings were recently published in the international journal Nature Communications. The research was patented in January 2022 as "Target biomarker detection method using a Dual antibody-linked immuno sandwich assay."