Online Ph.D Defence by Joakim Bastrup
Joakim Bastrup will defend his PhD thesis: "The molecular complexity of senile plaques in Alzheimer’s disease: Can it be modulated by a targeted antibody?"
01.05.2020 kl. 13.00 - 16.00
13.00 Opening by the Moderator
13.05 PhD lecture by Joakim Bastrup
14.00 Questions and comments from the Committee
Questions and comments from the audience at the Moderator’s discretion
16.00 Conclusion of the session by the Moderator
Due to the current circumstances the Ph.D defence will take place online via Skype for Business. If you wish to attend, please send an email to Kristine Uldal Knudsen before 29. april 2020 at 12:00.
The Faculty Council has appointed the following adjudication committee to evaluate the thesis and the associated lecture:
Professor Ole Nørregaard Jensen
University of Southern Denmark
Associate Professor Ann Brinkmalm
University of Gothenburg
Professor Jens Brøndum Frøkjær
Aalborg University Hospital
Associate Professor Ove Wiborg
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by neuronal loss and progressive accumulation of neurofibrillary tangles and senile plaques in the brain. Senile plaques are composed mainly of 38-43 residue amyloid beta-peptides (Aβ). The deposition of senile plaques occurs in the initial stages of AD, highlighting an association between senile plaques and initiation of biological events that could trigger the pathological events in the disease.
This PhD thesis set out to investigate the molecular composition of senile plaques on both peptide and protein levels, including modified forms of Aβ species and co-localizing proteins. The analysis was performed with two optimized tissue-based approaches, matrix-assisted laser desorption-ionization (MALDI) imaging and an microproteomic approach, combining laser microdissection and liquid chromatography-mass spectrometry (LC-MS/MS). Initial experiments were performed both on senile plaques from AD brains and from transgenic mouse model of AD, the APPPS1-21 mice, that express mutations causing a familial form of AD. Further, the two approaches were used to identify novel co-localizing proteins in senile plaques from APPPS1-21 mice and to elucidate whether treatment with an antibody targeting Aβ species could change senile plaque composition and co-localized protein profiles in APPPS1-21 mice.
In MALDI imaging, the addition of phosphoric acid to the “super-DHB” matrix significantly improved the signal-to-noise ratio of Aβ1-42, the main constituent of senile plaques. Additionally, the data indicated differences in the peptide composition of Aβ species in senile plaques isolated from AD and APPPS1-21 brains. The microproteomic approach identified 555 proteins co-localizing with senile plaques in APPPS1-21 mice. These proteins were identified to associate with engaging glia cells and degradation processes by pathway analysis. Furthermore, our analysis enabled identification of shared and uniquely expressed post-translational modifications (PTMs) on proteins co-localizing with senile plaques. Chronic treatment with an anti-Aβ antibody showed significant reduction of senile plaque load in hippocampus of APPPS1-21 mice. The microproteomic analysis allowed identification of proteins associated to different pathways when comparing to vehicle treated APPPS1-21 mice. Together, this PhD thesis provides novel data of the complex plaque-brain environment in APPPS1-21 mice and could be informative for future treatment strategies targeting senile plaques in AD.
HST - Department of Health Science and Technology
Skype for Business
29.04.2020 kl. 12.00