The doctoral dissertation in the field of Neuropathology will be examined at the Faculty of Health Sciences at Kuopio Campus. The public examination will be streamed online.
What is the topic of your doctoral research? Why is it important to study the topic?
My doctoral research studies the interaction of the brain's own immune cells, microglia, with amyloid plaques in Alzheimer's disease (AD) pathology in the finest detail. Understanding how microglia react to the plaque might be a key to understanding neurodegeneration around some plaques that microglia fail to remove.
What are the key findings or observations of your doctoral research?
We found that microglia react to the amyloid plaque based on chemical and physical properties of the plaque itself. Bigger plaques have more microglia clustered around them, but the microglial action towards the plaque is also different when compared to smaller ones. Microglia interact with the plaque primarily with their processes, and for plaques of about 15 µm in diameter, microglia have special thick processes which they dive into the centre of the plaque, condensing and encapsulating its core. We gave those special microglia interaction a working name ’snowploughers’.
We also showed that the common nuclear dye DAPI is also a reliable stain for dense core plaques in AD pathology. It can replace Thioflavin S which requires a complicated staining protocol and is harsh for the specimen.
The analysis of about 100 amyloid plaques proved that microglia clustered around them are mainly attracted to the plaque cores, ignoring the surrounding diffuse amyloid halo. The finding is compatible with the idea that microglia condense harmful loose fibrillar amyloid into inert dense cores. We also showed that ApoE protein encases the plaque core and is tightly connected with activated thick microglia processes. It shows that ApoE, a key protein in AD pathology, might be the main chemoattractant of the microglial processes to the plaque core, opening the way for new targeted therapies.
What are the key research methods and materials used in your doctoral research?
We worked on 6- and 13-month-old female APP/PS1 transgenic mice, a common AD model. We crossbred them with mice that express green fluorescent protein in their microglia, which help us see even the thinnest of microglia processes. We worked on 35 or 100 µm sections of the hippocampus, a brain structure that is especially vulnerable in AD.
By combining blue, green and red fluorescent histological stainings, we were able to see co-localization of three structures in the section at the same time. In addition, by taking large image stacks in the thick sections, we could see the position of microglia around the plaques in 3D.
Imaging was performed at UEF’s Cell and Tissue Imaging Unit in Kuopio with their state-of-the-art confocal microscope. We used the recently acquired IMARIS software for 3D image rendering.
The doctoral dissertation of Maria Gotkiewicz, MSc, entitled 3D confocal microscopy reveals new details of microglia-amyloid plaque interactions in APP/PS1 mouse model of Alzheimer's Disease will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Professor Melissa E. Murray from the Mayo Clinic Jacksonville, FL, USA and the Custos will be Professor Heikki Tanila from A. I. Virtanen Institute at UEF. The public examination will be held in English.
For further information, please contact:
Maria Gotkiewicz, MSc, [email protected], https://uefconnect.uef.fi/en/maria.gotkiewicz/
