Human episodic memory, a high-order cognitive function which allows us to voluntarily store and recall personal incidents that uniquely define our lives, share common memories and teach others what we have learned, is critical for survival and is a prerequisite for the development and transmission of human cultures. Clinical studies suggest that episodic memory depends on structures of the mesial temporal lobe including the hippocampus. Furthermore, vulnerability and progressive degeneration of neuronal cells in the hippocampus are hallmarks of Alzheimer’s disease, the most common cause of disabling memory problems in older persons. Importantly, both physiological episodic memory capacity and Alzheimer’s disease are heritable and polygenic, thereby amenable to human genetic studies.

In the present application I propose to investigate the genetic underpinnings of human episodic memory and of Alzheimer’s disease. Specifically, I propose to:

• Identify novel naturally occurring genetic variations related to human memory by means of whole-genome association and gene expression studies,
• Investigate patterns of genes related to episodic memory and Alzheimer’s disease,
• Visualize gene-dependent effects on human brain function by functional magnetic resonance brain imaging (fMRI) and by positron emission tomography (PET).

Importantly, DNA from well-characterized human populations is already available and all of the required laboratory techniques have been successfully used by my group and by my collaborators during the last three years of my SNF-professorship. Therefore, the present proposal for the continuation of the SNF-professorship is feasible, is guided by the knowledge acquired during the past three years and will expand the current knowledge by identifying novel genes and molecular pathways related to human memory and to Alzheimer’s disease. Ultimately, the identification of genes accounting for the variability of physiological and disease-related memory processes will provide new insights into the genetic basis of these polygenic phenotypes. I hope that my research will contribute to the development of targeted treatment of diseases involving memory disturbances by identifying relevant genetic pathways in humans.