Quantification of two fluorophores' concentration ratio in a mice model in preparation for a proposed method for early detection of Alzheimer's disease

Abstract

Many biomedical applications require concentration measurements of biological compounds, which may be achieved using targeted fluorescent probes. It has been shown that the ratio between amyloid-Beta and tau protein in the cerebrospinal fluid (CSF) is a good indicator of incipient Alzheimer's disease (AD).We have previously proposed a method that can accurately estimate the concentration ratio of these two proteins without the need to collect CSF samples: Fluorescent probes are injected to the blood and bind to the CSF biomarkers. A miniature needle with an optical fiber excites the fluorescent probes and collects the fluorescence emission. The concentration ratio between the proteins is estimated, and used for diagnosis of incipient AD. We present here the results of the method's concentration ratio estimation during trials performed on mice. Miniature tubes containing two fluorescent probes in several concentration ratios were implanted in two locations in the mice: subcutaneously, and deeper in the abdomen. The fluorescent probes were excited and the fluorescence intensity was measured. The concentration ratios were estimated from the fluorescence intensities with an average error of less than 20%. This study is a step towards the demonstration of the method in in vivo studies in mice with markers in the bloodstream/CSF.