Home Medizin Studie deckt Mutation auf, die das Fortschreiten der Alzheimer-Krankheit beeinflusst

Studie deckt Mutation auf, die das Fortschreiten der Alzheimer-Krankheit beeinflusst

von NFI Redaktion

Research coordinated by José Luis Royo, a scientist at the medical faculty of the University of Malaga, summarizes eight years of research and brings together 100 multidisciplinary specialists to identify a mutation that alters the course of Alzheimer’s disease.

Published in the „Journal of Alzheimer’s Disease,“ this study characterizes a genetic variant in the SIRPβ1 gene that affects the way the immune system fights beta-amyloid deposits, the cause leading to this pathology.

Conducted as part of this work was a longitudinal study with epidemiological samples from over 1,300 patients from Malaga and Barcelona, demonstrating the role of this mutation in the cognitive decline of those affected. However, it was found not to be a risk factor for Alzheimer’s disease per se.

„All people have the same genes, but there are variations of each that distinguish us. Different appearance and also different physiology and metabolism.“

José Luis Royo, Professor in the Department of Surgical Specialties, Biochemistry, and Immunology

The UMA scientist points out that an analysis of the presence of this variant in the SIRPβ1 gene revealed that 30% of the general population have one copy of the mutation, and 4% of the population have both copies affected. „So, we are talking about a variant that is very present in the general population,“ he says.

Dual Effect

The research, involving scientists from more than 50 different institutions, shows that the mutated variant alters the structure of the protein and how this affects the behavior of immune cells in the brain, known as microglia.

„When we examined their role in the course of the disease, we found that depending on the stage of the disease, the mutation has a dual effect: at the beginning, in patients with mild cognitive impairment, the mutation increases the risk of conversion to Alzheimer’s disease.“ In early stages, it has a detrimental effect; however, once dementia is established, these mutation carriers show a slower cognitive performance decline, indicating a positive effect in these patients,“ clarifies the UMA researcher.

Royo emphasizes that the mutation influences the immune system’s response to beta-amyloid deposits, likely affecting the neuroinflammation process, which is a physiological response in the early stages but becomes harmful if it becomes chronic during the course of the disease.

Therefore, the double effect of the genetic variant suggests that this cell signaling pathway should be inhibited in the early stages of the disease but stimulated in more advanced stages in order to mimic the effect generated by the mutation chemically. „This discovery opens the door to a new biochemical therapeutic target that could be synthesized into a drug in the future,“ he concludes.

Researchers are currently working to further characterize the effect of this mutation at a higher level of complexity and have developed a system to search for modifiers of this cell signaling pathway.

Multidisciplinary Scientific Team

„An insertion in SIRPβ1 shows a dual effect on the cognitive decline of Alzheimer’s disease and alters microglia response“ is a multidisciplinary work involving 100 researchers from more than 50 different institutions, including the Andalusian Institute of Neuroscience (IANEC) in Malaga, the Faculty of Science at UMA, the ACE Foundation, the Center for Genomic Regulation (CRG) in Barcelona, the Institute of Biomedicine in Sevilla (IBIS), the Andalusian Center for Developmental Biology (CABD), and many others.


Journal Reference:

García-Alberca, JM, et al. (2024). An insertion in SIRPβ1 shows a dual effect on the cognitive decline of Alzheimer’s disease and alters microglia response. Journal of Alzheimer’s Disease. doi.org/10.3233/jad-231150.

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