PhD student - Hyperspectral retinal imaging as a novel diagnostic biomarker for Alzheimer's disease

The Alzheimer’s disease (AD) research field has increasingly focused on the identification, development and validation of new diagnostic and prognostic biomarkers for AD. This endeavour is stimulated by the fact that the pathological changes of AD in the brain occur gradually over 20-30 years before the onset of symptoms. Therapies to delay or prevent AD are therefore increasingly aimed at these preclinical stages of the disease. However, this requires early diagnosis of AD. Current methods to identify individuals with presymptomatic AD, such as positron emission tomography and cerebrospinal fluid analysis are expensive, invasive and not scalable at a population level. Accordingly, there is an urgent need for low cost, minimally invasive and widely available screening and diagnostic tests. Retinal imaging offers the ideal solution.

The retina is an integral part of the central nervous system and many of the characteristic pathological processes that occur in the AD brain are also found in the retina. With the availability of non-invasive, high-resolution imaging techniques, it offers “a window to the brain”. Together with two other research groups, we have delivered pioneering evidence for the use of hyperspectral retinal imaging (HSRI) to detect retinal amyloid burden and thereby identify people at risk of AD. We now seek to assess whether HSRI could be used as a tool for AD screening. Key outstanding questions that we want to address in this research project are related to the specificity of the technique, and include: (1) What is the molecular basis of the HSRI signal of AD? (2) Can HSRI be used to distinguish AD from other dementias?

You will perform preclinical research, aiming to advance our understanding of the neuropathological changes that occur in the AD retina and to determine the molecular basis of the HSRI signal. Thereto, we will perform HSRI of synthetic amyloid conformational forms, and in cellular and mouse models of proteinopathies (amyloid, Tau, alpha-synuclein) and correlate these data will molecular assays of protein oligomerisation/aggregation. All research runs within the ‘Vision Core Leuven’, a preclinical animal platform which brings together cutting-edge technologies within the field of ocular imaging, electrophysiology and visual function testing in laboratory animals (https://www.visioncore.be). Furthermore, we employ state-of-the-art techniques for detailed morphological phenotyping, including confocal/multiphoton/light-sheet microscopy, optical clearing and time-lapse imaging, and longitudinal and post-mortem morphometrical analyses to follow inflammatory and degenerative processes.