The role of neuroinflammation in Alzheimer's disease

Petronella Kettunen

To: Oxford University, UK

From: University of Gothenburg

Project abstract

The lack of treatments of age-related disorders, such as Alzheimer's disease (AD), is a global challenge today with the increased life expectancy. Academia, clinicians and companies need to join their efforts to develop diagnostics for early detection and new treatments. To this end, we have initiated a collaboration between University of Gothenburg (including the newly formed Centre for Cognitive Medicine, CCM) and University of Oxford, the university hospitals Sahlgrenska Hospital in Gothenburg and John Radcliffe Hospital in Oxford, and pharmaceutical companies in Oxford.

The goal in this project is to target neuroinflammation in AD to understand the causes of the disease and identify targets for future drug development. The Department of Neuropathology in Oxford is host to one of the largest brain tissue collections in the UK, the Thomas Willis Brain Bank. In this project, the preclinical and clinical parts are closely linked; the target genes will first be evaluated in the patient material in Oxford and then in a new zebrafish model back in Gothenburg after the project period. The zebrafish model will also be used in future drug discovery in collaboration with companies in Oxford and Region Västra Götaland. Future clinical trials will be performed in collaboration with clinicians at CCM and hospitals in Region Västra Götaland.

The researcher, Dr Petronella Kettunen, will spend 12 months in Oxford working with the clinical material and acquire skills in innovation and management highly relevant for current and future success of the project, at Said Business School.

Summary results

Project outcomes: The number of patients affected by dementia, such as Alzheimer's disease (AD), will grow with the increased life expectancy. However, we lack precise diagnostic methods that can distinguish between dementia subtypes and appropriate treatments for those affected by these diseases. Neuroinflammation, mediated by the immune cells of the brain, microglia, has emerged as a promising pathological mechanism for memory impairments and neurodegenerative disorders, including AD. Therefore, target pathways involving neuroinflammation have potential to serve critical roles in future diagnostic tools and treatments for dementias.

The goal of this project has been to establishing new contacts between University of Gothenburg and University of Oxford, as well as providing new genetic and molecular knowledge on the role of neuroinflammation in the disease process of AD and other dementias. During the project period, Dr Kettunen has acquired new research methods and medical topics that have allowed her perform her project successfully. The clinical findings in this project have generated new gene candidates related to microglia function that will now be followed up with mechanistic analyses in the zebrafish in Dr Kettunen's lab in Gothenburg.

Moreover, the research findings, research collaborations and acquired knowledge during this period has been directly instrumental in providing new funding, data for future grant applications, as well as attracting new students and research fellows to her lab in Gothenburg. The project has generated two published papers, four submitted manuscript and three manuscripts under development. During the project period, the contact with the private sector has been strengthened, resulting in the development of two collaborative projects with companies in Oxford and in Gothenburg. In addition, the project has strengthened her position in collaboration with the health-care sector, leading to new opportunities. Finally, the collaborations and project output will be of great importance for Dr Kettunen in her continuing work as a co-director at the Centre for Cognitive Medicine in Gothenburg and as a board member of the Swedish Association for Cognitive Medicine.

Education/outreach: Dr Kettunen has given a number of lectures at University of Oxford and at University of Gothenburg during the project period. She has also organized her PhD course in Learning and memory, two public seminars for the Centre of Cognitive Medicine in Gothenburg and has been part of the organizing committee for the conference Brain Networks in Gothenburg. She was also elected to the board of the Swedish Association of Cognitive Medicine to continue her work with collaboration between academia and the health-care sector, and public outreach in this field. During her time in Oxford, she has supervised four PhD students out of which three graduated during the spring 2016, and mentored four postdocs in her lab in Gothenburg. She has also attracted eleven new postdoc candidates to her lab, out of which four were selected to apply for individual fellowships to join her lab.

Career development: Dr Kettunen has participated in several local and international conferences within the field of dementia during the project period. She has also participated in excellent courses focusing on drug discovery, medical statistics, project management and business development at University of Oxford and in a unique transforming leadership course at the renowned Saïd Business School in Oxford. The training has provided her new tools as a research leader and innovator.

Finally, the project has built long-lasting collaborations between the academic, health-care and private sectors of Region Västra Götaland and the Oxford region. It has provided new clinical findings supporting the role of neuroinflammation in Alzheimer's disease which will be instrumental in the development of future diagnostics, preventions and treatments for Alzheimere's disease and other dementias.