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On the nature of mixed neurodegenerative amyloidopathies

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Author

  • Nadja Gustavsson

Summary, in English

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases in the world. It has been possible to identify common denominators for AD and PD, including aggregation of the amyloid proteins amyloid-beta (Aβ) and alpha-synuclein (α-syn). Given the continued challenges in finding therapies that could stop or prevent proteinopathies such as AD or PD, it is apparent that our knowledge of the most common neurodegenerative diseases remains incomplete. Therefore, there is a pressing demand to better understand the molecular mechanisms, for which novel methods and disease models are needed. In this thesis, we generated novel models to study experimentally protein aggregation in PD and AD; (1) induced pluripotent stem cells (iPSC) expressing a familial PD-linked mutation in the GBA gene, (2) idiopathic and familial PD patient derived midbrain spheroids, and (3) a mouse model of mixed amyloidosis of aggregated α syn and Aβ. Furthermore, we applied a novel approach to study protein aggregation, by combining spectroscopy methods such as Optical Photothermal Infrared (O-PTIR) and synchrotron-based X-ray fluorescence (S-XRF), to image neuronal cells and to characterize the aggregate structures and distribution. Our novel methodological approach allows for imaging of the same samples from different perspectives by studying cells with the light of different wavelengths. The cell models could be beneficial to develop patient-specific treatments, as well as study early, pre-symptomatic, molecular changes in patient brain cells. Likewise, our novel mouse model of in vivo aggregation could further provide insight into early molecular mechanisms triggering amyloid aggregation related to AD and PD.

Publishing year

2021

Language

English

Publication/Series

Lund University, Faculty of Medicine Doctoral Dissertation Series

Issue

2021:104

Document type

Dissertation

Publisher

Lund University, Faculty of Medicine

Topic

  • Neurosciences

Keywords

  • Medicin och hälsovetenskap
  • Parkinson's disease (PD)
  • Alzheimers disease (AD)
  • Amyloidosis
  • Alpha synuclein
  • Amyloid beta

Status

Published

Research group

  • Medical Microspectroscopy

Supervisor

ISBN/ISSN/Other

  • ISSN: 1652-8220
  • ISBN: 978-91-8021-111-6

Defence date

21 October 2021

Defence time

08:00

Defence place

Join by Zoom: https://lu-se.zoom.us/j/64587067982?pwd=azAyY1ZLTUtFdEN2dUY3ZUl4RHBEZz09

Opponent

  • Vittorio Bellotti (Professor)