Inmaculada Cuchillo Ibáñez will lead a project to study the role of apoE protein glycosylation in Alzheimer’s disease

26 de February de 2025

  • The researcher from the Institute for Neurosciences UMH-CSIC has received a $300,000 grant from the Alzheimer’s Association to study the relationship between the apoE protein and Alzheimer's disease over three years.
  • The team will use advanced glycoproteomics techniques and stem cells to gain a better understanding of this neurodegenerative disease.

Photo: Inmaculada Cuchillo Ibáñez, researcher at IN UMH-CSIC.

Studying the function of the apoE protein from a functional perspective—beyond its role as a genetic risk factor for developing Alzheimer's disease—is the goal of the new project led by Inmaculada Cuchillo, funded by a $300,000 grant from the Alzheimer’s Association. The researcher, part of the Altered Molecular Mechanism in Alzheimer’s Disease and Dementia group at the Institute for Neurosciences (IN), a joint center of the Miguel Hernández University (UMH) in Elche and the Spanish National Research Council (CSIC), will conduct an innovative three-year study on apoE protein glycosylation and its impact on neurodegenerative diseases, in collaboration with researcher Javier Sáez Valero.

Glycosylation is an essential biological process in which sugar molecules are added to proteins, modifying their structure and function. This phenomenon is crucial for proteins to reach their correct destination within the cell and properly fulfill their role. “Eighty percent of proteins are glycosylated, yet we know very little about how this process affects their functions”, explains Inmaculada Cuchillo. In the case of apoE, a key protein in lipid transport, including cholesterol, and the pathophysiology of Alzheimer’s disease, previous studies suggest that modifying its glycosylation could impact its function, potentially opening new therapeutic avenues.

The study will begin next April and will be carried out in several phases. First, the glycosylation of apoE will be analyzed in human samples, including the cerebral cortex and cerebrospinal fluid, using advanced glycoproteomics techniques in collaboration with the biotechnology company Asparia Glycomics, led by Niels Reichardt. In the next phase, glycosylation will be modified in astrocytes and neurons differentiated from induced pluripotent stem cells (iPSCs), provided by Carlos Vicario, a researcher at the Cajal Institute (CSIC). This phase aims to assess this process's impact on key cellular functions, such as cholesterol transport and the clearance of beta-amyloid peptide, which forms the characteristic amyloid plaques in Alzheimer's disease.

Additionally, the team will work with human samples through collaboration with Henrik Zetterberg, a researcher from the University of Gothenburg (Sweden), as well as Pascual Sánchez and Alberto Rábano, researchers from the tissue bank at the Fundación CIEN. These collaborations will enable the team to conduct experiments using samples from patients at different stages of the disease.

“This project represents a significant step in my research, as it will allow me to explore a largely unexplored field with great potential for understanding Alzheimer's disease from the functional perspective of apoE, beyond its role as a genetic risk factor”, emphasizes Inmaculada Cuchillo. In this regard, the researcher notes that it is an ambitious study made possible by using cutting-edge technologies available at IN UMH-CSIC, such as state-of-the-art flow cytometry, confocal microscopy, and human neuron and astrocyte cell cultures.

The Alzheimer's Association is a leading U.S. organization in funding research on Alzheimer's disease and other dementias. Through its grant programs and international collaborations, it fosters innovative studies aimed at better understanding this pathology and developing more effective treatments for patients. Its commitment to science has contributed to advancing knowledge of the genetic, biological, and environmental factors that influence the progression of Alzheimer's."

Source: Institute for Neurosciences UMH-CSIC (in.comunicacion@umh.es)