Instrufoundation Fellow grant supports research into the cellular role of genetic risk factors in Alzheimer's disease

Neurological diseases are complex and remain poorly understood. Although recent studies have identified genetic regions containing mutations that influence disease susceptibility, linking these genetic changes to disease mechanisms remains a significant challenge.

"This gap limits our understanding of the factors influencing disease onset and progression, as well as the development of effective treatments for conditions such as Alzheimer's disease," notes Dr. Mikael Marttinen, a researcher at Tampere University.

According to Marttinen, a critical issue is insufficient knowledge about how genetic regions regulate brain cell functions and how disruptions in these processes contribute to diseases. His research presents a novel approach to investigating the cellular functions regulated by these genetic regions and mapping their connections to pathological features in the human brain.

Marttinen's study aims to map regulatory regions to brain cell functions and pathological features of neurological diseases using advanced single-cell and spatial analysis technologies combined with deep learning modeling.

The research project includes professors Matti Nykter and Pasi Kallio, as well as associate professor Xin Lai from Tampere University. International partners include Judith Zaugg from the University of Basel and Mor Nitzan from the Hebrew University of Jerusalem.

Identifying changes that increase disease risk and understanding why

Mikael Marttinen’s interest in the genetic mechanisms of Alzheimer's disease began during his master's studies. Since then, his research career has been guided by innate curiosity. "Each discovery opens the door to new questions, and the next doors are waiting to be opened," he says.

Marttinen's doctoral research focused on identifying brain changes associated with the accumulation of protein deposits characteristic of Alzheimer's disease. He was particularly interested in mapping changes occurring in the early stages of the disease. "This information is also crucial from a drug development perspective," he notes.

In 2019, Marttinen received his first grant from the Instrumentarium Science Foundation for research related to this topic. It enabled him to undertake a three-year postdoctoral position at the prestigious European Molecular Biology Laboratory (EMBL) in Germany. At EMBL, he developed methods to study the regulatory roles of non-coding genomic regions, which constitute over 90 % of the genome and harbor many Alzheimer's disease risk mutations.

"I developed methods to study gene regulatory mechanisms at the single-cell level, opening new opportunities for understanding the disease," he explains.

His experience at EMBL provided Marttinen with valuable networks and new research insights.

"Working abroad opened my eyes to how top-tier research operates globally and what drives breakthrough results. It’s not just about funding but also about ambitious people and bold thinking."

Instrufoundation Fellow grant essential for assembling a research team

Upon returning to Tampere, Marttinen combined expertise from his doctoral research with the methods developed at EMBL into a new spatial approach. He now studies cellular models and tissue samples, precisely mapping cellular functions, locations, and interactions. "By integrating these approaches, we can model the effects of genetic risk mutations and relate them to the spatial context of cells, for example, examining how they influence cellular functions near Alzheimer's disease-related amyloid plaques," he explains.

The €150,000 Instrufoundation Fellow grant Marttinen received in February 2025 facilitates the expansion of his research.

"It allows me to recruit researchers to my team and conduct new experiments, thereby continuing our investigations into the mechanisms behind neurodegenerative diseases," he says.

Marttinen emphasizes the many unresolved questions in neurodegenerative disease research. His vision is to determine how genetic risk factors increase an individual's susceptibility to conditions like Alzheimer's disease. Such knowledge could lead to the development of more effective and personalized treatments.

Text: Tia Härkönen
Picture: Tampere University