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Doctoral defence of Riikka Lampinen, MSc, 25 Nov 2022: New observations about mitochondrial alterations in Alzheimer’s disease

The doctoral dissertation in the field of Neurosciences 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?

Alzheimer’s disease is a progressive neurodegenerative disease in which prevalence increases with age. Genetic, environmental and lifestyle factors are associated with an increased risk for Alzheimer’s disease. However, the exact cause of Alzheimer’s disease is not yet completely understood. Given that the brain pathology in Alzheimer’s disease has been estimated to start even decades before the first clinical symptoms, the key for treating this disease will be an early intervention. For example, olfactory impairment has been frequently reported as one of the first symptoms in individuals living with Alzheimer’s disease. Furthermore, dysfunction of cell mitochondria has been previously linked both to aging and Alzheimer’s disease.

What are the key findings or observations of your doctoral research?

This doctoral thesis composed of three studies investigating mitochondrial dysfunction in non-neuronal cells in Alzheimer’s disease.

Study I focused on exploring alterations in transfer and degradation of mitochondria between the neurons and astrocytes of the brain. As the main result, the thesis demonstrated that astrocytes derived from mice modelling Alzheimer’s disease or from human induced pluripotent stem cell culture models of Alzheimer’s disease internalized and degraded significantly more neuronal mitochondria compared to control astrocytes. The internalization and degradation of the neuronal mitochondria were further increased in astrocytes derived from aged mice modelling Alzheimer’s disease. To our knowledge this is the first report for altered transmitophagy in Alzheimer’s disease.

Study II and III investigated Alzheimer’s disease related alterations in cell cultures of olfactory mucosa cells derived by biopsy from individuals with Alzheimer’s disease or mild cognitive impairment and cognitively healthy controls. The olfactory mucosa cells derived from individuals living with Alzheimer’s disease displayed altered mitochondrial function, homeostasis of biometals, and several Alzheimer’s disease -related gene-expression changes when compared to the controls.

How can the results of your doctoral research be utilised in practice?

Only little is known about the intercellular degradation of mitochondria, transmitophagy, in Alzheimer’s disease. The results of this doctoral thesis create a foundation for even more mechanistic studies on this topic. Furthermore, the results of studies II and III emphasize the potential of olfactory mucosa cells to be used as a human-based research model for Alzheimer’s disease.

What are the key research methods and materials used in your doctoral research?

This doctoral thesis was performed mainly in the research group of Associate Professor Katja Kanninen at the A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland. This research utilized multiple different research models methods including for example primary cell cultures, immunohistochemical stainings, fluorescence- and confocal microscopy, single-cell RNA-sequencing, assessment of intracellular levels of metals and assays for mitochondrial function.We collaborated with experts on memory-related disorders and otolaryngology from the Kuopio University Hospital and the Brain Research Unit of the University of Eastern Finland in two of the studies. Furthermore, in the beginning of my doctoral studies I visited Associate Professor Antony White’s research group in QIMR Berghofer Medical Research Institute, Australia for two months to learn methods for culturing the cells of the olfactory mucosa. Study II is part of the EU Horizon 2020 research project ”Transport derived Ultrafines and the Brain Effects” (TUBE).

I would like to express my gratitude for all the individuals and their family members who participated to this study, and to all the funding sources. Without their participation, commitment, and support this research could have not been performed.

The doctoral dissertation of Riikka Lampinen, MSc, entitled Mitochondrial Dysfunction in Non-Neuronal Cells in Alzheimer's Disease will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Associate Professor Evandro Fei Fang of the University of Oslo and Akershus University Hospital, and the Custos will be Associate Professor Katja Kanninen of the University of Eastern Finland.

Public examination

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Doctoral dissertation

For further information, please contact:

Riikka Lampinen, MSc, riikka.lampinen (a) uef.fi