Prof. Dr. Alfredo Ramirez

Age-related cognitive disorders, like Alzheimer’s disease, are phenotypes resulting from complex interactions between risk factors like genetics, epigenetics, and environment. Delineation of these factors will translate into personalized treatment and better prevention strategies.

Our research: The division of Neurogenetics is interested in understanding the complex (epi)genetic architecture modulating the disease processes underlying neurodegenerative dementias and age-related cognitive disorders. To this end, our main focus is on the development and implementation of innovative and robust methods to identify and characterize genetics and epigenetics factors influencing the risk of these disorders. Reaching this goal is only possible because the division has access to genetic and epigenetic data from several thousands of individuals.

Our goals:

1) Identification of novel genes and pathways related to cognitive disorders. For this, the division has access to genetic data from more than 90,000 European samples of AD cases and healthy controls. This unique setup provides a statistical power that allowed us already to double the number of known genetic risk factors for AD. Currently, we are in the process of expanding this list.

2) Development of novel approaches to explore the genetic architecture modulating the rate of disease progression of AD. To achieve this goal, the division leads the largest European initiative dedicated exclusively to genetic research on disease progression in early stages of AD, i.e., mild cognitive impairments (MCI, ~9,000 cases). In this context, the division is establishing state-of-the-art analytical methods to model and analyze longitudinal phenotypes combined with genetic data.

3) Generation of additional layers of “omics” data. Presently, the division has biobanked several thousands of biomaterials from patients affected by cognitive diseases in which biological consequences of genetic variants associated with the disease can be readily explored via metabolomics and/or proteomics.

Our successes: Combining existing datasets, our group has been crucially involved in several international efforts leading to the identification of several new genetic loci modulating the risk of Alzheimer’s disease. Importantly, we have also defined that a genetic risk variant for Alzheimer’s disease is also modulating the speed with which the disease progress over time. Beyond genetics, our group has also participated in the identification of novel blood and cerebrospinal fluid proteins and metabolites that might serve as biomarkers for Alzheimer’s disease. All these findings have clear translational potential for early detection and prevention strategies for Alzheimer’s disease.

Our methods/techniques:

• Our group uses genome-wide association studies in form of genetic variants or methylation data as the main tool to search for molecular underpinning of age-related cognitive disorders
• Our group is also interested in developing novel mathematical and statistical methods to analyze genetics and epigenetics of cognitive decline.
• We also perform integrative analysis of GWAS datasets and deep-sequencing datasets within the framework of international collaborations.
• Our team also combine different available “omics” datasets to perform integrative analyses aiming at the identification of predictive patterns of disease progression in predementia stages of Alzheimer’s disease.