Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by memory loss and cognitive decline. These symptoms are associated with pathological changes in the brain, primarily the accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles composed of tau protein. Current diagnostic approaches are largely invasive and are typically used only after the onset of clinical symptoms, highlighting the need for accessible and early detection methods.
The aim of this project is to develop a novel, minimally invasive method for detecting AD biomarkers in blood plasma using a simple and widely accessible analytical technique. The approach is based on the design of small fluorescent molecular probes that selectively bind to Aβ and tau aggregates present in plasma. Upon binding, these probes produce a characteristic fluorescence signal that can be easily measured, enabling sensitive detection of disease-related biomarkers.
A key innovation of this project is the use of advanced computational tools—including machine learning, artificial intelligence, molecular modelling, and quantum chemical methods such as (TD)-DFT—to guide the design and optimization of these probes. Candidate molecules will be evaluated through in vitro assays to assess their selectivity and binding affinity toward Aβ and tau aggregates, followed by in cellulo studies to examine their performance in more complex biological environments. Proof-of-concept validation will also include ex vivo testing on post mortem brain tissues from AD patients.
To enhance detection sensitivity, particularly given the low concentrations of biomarkers in blood, the project will employ magnetic nanobeads for biomarker enrichment via magnetic separation. Additionally, gold nanorods will be used to amplify fluorescence signals, further improving detection limits. Quantitative analysis will be performed using flow-induced dispersion analysis (FIDA), enabling precise measurement of biomarker concentrations.
The project brings together a multidisciplinary consortium of ten research institutions, combining expertise in chemistry, nanotechnology, medicine, and computational science. Among them is also dr. Slavko Kralj from Jožef Stefan Institute.
