CNS protein aggregates: multimodal scope for early detection
- Reference number
- UKR24-0022
- Project leader
- Skoryk, Valeriia
- Start and end dates
- 241227-261226
- Amount granted
- 998 438 SEK
- Administrative organization
- Lund University
- Research area
- Life Sciences
Summary
Main objectives. The project proposes to validate a combination of cutting-edge imaging techniques that allow earlier detection of CNS protein aggregates in AD by leveraging the unique structural fingerprints they present. Condensed work plan. To create an integrated multimodal, interdisciplinary study of amyloid structure–toxicity–compounds–localization/organ environment interplay, we propose gaining insight into early protein aggregates in a continuous brain and spinal cord volume at a subcellular level. We acquire data from the same sample at high resolution from X-ray tomography followed by multiscale structural analysis (infrared spectroscopy, multiplex immunolabeling). Then, by creating a 3D reconstructed model of an organ, where data from all instruments will be correspondingly overlayed, we provide a spatial understanding of protein aggregates within the sample. Included in the project, complementary downstream immunohistological experiments will allow us to integrate results from multidimensional datasets into clinically relevant settings. This will help better understand multifactorial amyloid diseases, ultimately allowing new therapeutic opportunities. Expected results: a detailed "fingerprint" of the protein aggregates – multimodal (spectroscopic, tomographic & histopathologic) profile of different protein aggregates addressing a gradient of structural changes and compounds variation in AD and non-AD samples in CNS (both brain and spinal cord).
Popular science description
In the backdrop of neurodegenerative disorders like Alzheimer's disease, protein aggregates within the central nervous system (CNS) play a central role, with dementia as the predominant symptom. The social costs of these disorders have been rising with the increasing number of affected individuals and reached 62.9 billion SEK in 2012. Detecting these aggregates early is pivotal for timely diagnosis and disease progression management. However, this task is immensely challenging due to the lack of sensitive methods capable of assessing the intricate complexity of protein aggregates within native tissue due to a myriad of interplay between structural variety, multiple components, and environmental influence. Our project's primary objectives revolve around validating state-of-the-art imaging techniques designed for the early detection of protein aggregates. We achieve this by harnessing early protein aggregations' unique structural and compositional characteristics compared to late-formed aggregates. Our comprehensive workflow utilizes X-ray (tomography) and visible or infrared (spectroscopy) light sources. It encompasses a multidisciplinary simultaneous exploration of amyloid structures, toxicity, compounds, and localization within the brain and spinal cord at a subcellular level, same as when the symphonic orchestra plays, we can recognize participated instruments all at once. Our expected outcomes will furnish a detailed 'fingerprint' of protein aggregates, shedding light on structural alterations and compound variations in Alzheimer's and non-Alzheimer's CNS samples.