Prof. Dr. Dr. Alfredo Ramirez
Adresse
Robert-Koch-Str. 10
50931 Cologne
Matrix Metalloproteinase 10 is a biomarker in cerebrospinal fluid associated with progression to dementia of the Alzheimer’s type
Miami plot for the two-stage Epigenome-wide association study on obsessive-compulsive disorders. The X-axis shows the genomic position. The Y-axis shows the nominal p-value for the discovery EWAS on a logarithmic scale, scaled by the coefficient sign in the same analysis. Horizontal red lines mark the 0.05 threshold for the discovery analysis. Purple dots represent the 310 CpGs that were significant at the replication stage. Dot size corresponds to the adjusted p-value in the replication stage on a logarithmic scale.
Cognitive (EPI)Genomics & Systems Biology
Short Introduction
The research group on Cognitive (EPI)Genomics & Systems Biology studies how genetic, epigenetic, and proteomic factors shape cognition and neurodegenerative disease, integrating multiomic and longitudinal data to advance early detection and translational interventions.
Research Focus
Our research group aims to understand how genetic, epigenetic, and proteomic mechanisms shape cognition and contribute to neurodegenerative dementias and age-related cognitive disorders. By integrating multiomic and longitudinal data from large cohorts, we seek to identify biological factors that influence disease risk, progression, and resilience.
Our main goal is to understand the mechanisms driving cognitive aging, emphasizing early detection and how brain and peripheral systems interact. We translate molecular research into clinical practice by analyzing cerebrospinal fluid and blood proteomics, including SASP markers, to investigate how systemic and brain-specific factors influence accelerated biological aging and Alzheimer’s disease progression. This approach advances our understanding of cognitive mechanisms and aids in developing personalized treatments, early diagnosis, and targeted therapies.
Our Goals
Identify and characterize the genetic and epigenetic factors that influence neurodegenerative dementias and age-related cognitive decline. Using integrative multiomic analyses and innovative, robust methodological approaches in collaboration with international research consortia, we aim to discover new genes and regulatory elements and understand how these factors modulate disease progression and individual cognitive trajectories, providing a foundational understanding of variability in cognitive aging.
Goal 2: Investigate Aging-Related Mechanisms and Brain-Periphery Crosstalk
Examine how proteomic signatures in cerebrospinal fluid and blood, including SASP markers, interact with genetic and epigenetic factors to accelerate biological aging and cognitive decline. By developing novel integrative analytical methods and collaborating with international consortia, this goal investigates the mechanisms linking central and peripheral systems and how these interactions impact disease progression and cognitive trajectories over time.
Goal 3: Enable Early Detection and Translational Interventions
Leverage longitudinal studies to identify genetic, epigenetic, and proteomic biomarkers that predict cognitive decline. Working closely with clinicians, we develop predictive models of disease progression and translate these findings into early detection strategies and treatment options. Our goal is to connect basic research with clinical applications to prevent or delay Alzheimer’s disease dementia and related disorders.
Selected Publications
Martino-Adami PV, Chatterjee M, Kleineidam L, ………………….., Wagner M, Schneider A, Ramirez A. Prognostic value of Alzheimer's disease plasma biomarkers in the oldest-old: a prospective primary care-based study. Lancet Reg Health Eur. 2024 Aug 16;45:101030. doi: 10.1016/j.lanepe.2024.101030.
- Dalmasso, MC, de Rojas, I, Olivar, N, …………………., Morelli, L#, Ramírez, A#. (2023). The first genome-wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease. Alzheimers Dement. 2024 Feb;20(2):1298-1308. doi: 10.1002/alz.13522.
- Campos-Martin R, Bey K, Elsner B, ………………, Wagner M, Ramirez A§. Epigenome-wide analysis identifies methylome profiles linked to obsessive-compulsive disorder, disease severity, and treatment response. Mol Psychiatry. 2023 Aug 16. doi: 10.1038/s41380-023-02219-4.
Jansen IE, van der Lee SJ, Gomez-Fonseca D, de Rojas I, Dalmasso MC, Grenier-Boley B, Zettergren A, Mishra A, Ali M, Andrade V, Bellenguez C, Kleineidam L, …………………………………., Hiltunen M, Ingelsson M, Andreassen OA, Clarimón J, Sleegers K, Ruiz A, Ramirez A*, Cruchaga C, Lambert JC, van der Flier WM. Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers. Acta Neuropathol. 2022 Nov;144(5):821-842. doi: 10.1007/s00401-022-02454-z.
- Bellenguez C, Küçükali F, Jansen IE, Kleineidam L, Moreno-Grau S, Amin N, Naj AC, Campos-Martin R, ……………………………………., van der Flier WM, Ruiz A, Ramirez A*, Lambert JC. New insights into the genetic etiology of Alzheimer's disease and related dementias. Nat Genet. 2022 Apr;54(4):412-436. doi: 10.1038/s41588-022-01024-z
Research Areas
RA-1: Identification of new biomarkers and pathomechanisms of metabolic diseases
RA-2: Central nervous regulation of metabolism