Studies Clarify How Proteins Connected to Alzheimer’s Disease Affect the Development of Neurons

The crucial role that the protein Contactin-4, which is produced by the gene CNTN4, plays in forming neurons has been identified by a recent study headed by the University of Exeter and published in Open Biology.

Although CNTN4 was recognized to have a part in autism, its functional roles were unclear, which is why the researchers started researching it. The group investigated the role of CNTN4 in the brain, specifically in relation to its interactions with proteins implicated in neurodegenerative illnesses such as Alzheimer’s disease.

The cortical region of the brain, which is in charge of important mental processes including memory, reasoning, and thinking, is where the CNTN4 gene is first deleted in mice. They discovered that the cortical area had a distinct neuronal development pattern.

The contact between the genes CNTN4 and APP, a gene significantly associated with Alzheimer’s disease, has been shown for the first time in human cells by researchers. This interaction reveals a co-dependent relationship that is crucial for brain development, particularly for the normal proliferation of neurons. They discovered that CNTN4 regulates CNTN4 expression through an interaction with APP in addition to contributing to neural elongation in the brain’s frontal cortex area.

Through research on genetically altered human cells, the group also found that CNTN4 and APP have a complicated relationship. When CNTN4 is eliminated, APP levels fall, but not completely. According to the experts, APP might make up for CNTN4’s loss and vice versa.

Lead author of the study Dr. Rosemary Bamford, University of Exeter Medical School, said: “It was quite remarkable to discover that CNTN4, a gene linked to developmental processes, also plays a role in modulating factors involved in Alzheimer’s disease. This intersection of developmental and neurodegenerative pathways offers exciting new insights into the broader implications of these proteins.”

 senior author Dr. Asami Oguro-Ando of the University of Exeter Medical School , stated, “Looking ahead, my group is keen to further dissect the molecular mechanisms underpinning the interaction between CNTN4 and APP and explore their wider implications for disorders like Alzheimer’s and autism spectrum disorder. Our next steps involve clarifying how the CNTN4-APP interaction impacts neural activity. Understanding this interaction is crucial as it represents a fundamental step towards a comprehensive grasp of neurodevelopmental and neurodegenerative disorders.”

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