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On the nature of mixed neurodegenerative amyloidopathies

Gustavsson, Nadja LU (2021) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Bellotti, Vittorio, University of Pavia, Italy
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Medicin och hälsovetenskap, Parkinson's disease (PD), Alzheimers disease (AD), Amyloidosis, Alpha synuclein, Amyloid beta
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2021:104
pages
74 pages
publisher
Lund University, Faculty of Medicine
defense location
Join by Zoom: https://lu-se.zoom.us/j/64587067982?pwd=azAyY1ZLTUtFdEN2dUY3ZUl4RHBEZz09
defense date
2021-10-21 08:00:00
ISSN
1652-8220
ISBN
978-91-8021-111-6
language
English
LU publication?
yes
id
7fed8089-28c3-4185-9a33-c62309c3b587
date added to LUP
2021-09-24 15:48:30
date last changed
2023-09-07 09:19:42
@phdthesis{7fed8089-28c3-4185-9a33-c62309c3b587,
  abstract     = {{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.}},
  author       = {{Gustavsson, Nadja}},
  isbn         = {{978-91-8021-111-6}},
  issn         = {{1652-8220}},
  keywords     = {{Medicin och hälsovetenskap; Parkinson's disease (PD); Alzheimers disease (AD); Amyloidosis; Alpha synuclein; Amyloid beta}},
  language     = {{eng}},
  number       = {{2021:104}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{On the nature of mixed neurodegenerative amyloidopathies}},
  year         = {{2021}},
}