Alzheimer's 'Spreading Pathway' Discovered... First Mapping of Molecular Circuits by Brain Region [Reading Science]

Tracking Dopamine and Serotonin Signal Changes
"Clues for Precise Diagnosis and Treatment Expected"

A domestic research team has, for the first time, identified a "molecular signaling circuit diagram" that shows how Alzheimer's disease spreads and progresses within the brain. By simultaneously analyzing changes in proteins and neurotransmitters, the team three-dimensionally revealed how Alzheimer's disease is interconnected and disseminated across various regions of the brain.

The Korea Brain Research Institute (KBRI) announced on the 18th that the research team led by Jonghyuk Yoon of the Degenerative Brain Diseases Research Group has mapped out a "molecular signaling circuit diagram" for each brain region according to the early progression of Alzheimer's disease, through integrated analysis of proteome and neurotransmitter data.

Overview of the Study on Identifying Alzheimer’s Disease Pathogenesis-Related Signaling Modules through Integrated Proteomic and Neurotransmitter Analysis of Seven Brain Regions in PS19 Tauopathy Mice. Provided by Research Team

Alzheimer's disease is a representative neurodegenerative disorder characterized by the abnormal accumulation of tau protein, as well as complex disruptions in various neurotransmitter systems, including dopamine and serotonin. However, previous studies have often focused on specific proteins or individual neurotransmitter changes, and thus, the way these factors are interconnected across brain regions to drive disease progression has not been fully elucidated.

To overcome these limitations, the research team adopted an "integrative multi-omics analysis strategy." Using PS19 mice—a model of tauopathy in Alzheimer's disease—they simultaneously analyzed changes in the proteome and neurotransmitters across seven key brain regions, including the hippocampus and cerebral cortex. With state-of-the-art data analysis techniques, they traced the structural connections between protein signaling networks and changes in neurotransmitter concentrations.

As a result, they found that dopamine- and serotonin-related signaling systems change in distinct ways depending on the brain region during Alzheimer's progression. In particular, in the hippocampus, which is responsible for memory and learning, and the cerebellum, which is involved in motor control, changes in neurotransmitters were found to be closely linked with specific protein signaling networks, affecting disease progression.

The research team explained that, through this work, they have elucidated the complex pathophysiology of Alzheimer's disease not simply at the level of molecular changes, but at the level of "molecular circuit diagrams" for each brain region.

Dr. Yoon stated, "This study is significant in that it presents a new perspective for understanding the pathophysiology of Alzheimer's disease at the circuit level of each brain region by integrating proteome and neurotransmitter data," adding, "We expect it will contribute to the development of novel diagnostic and therapeutic strategies based on integrative multi-omics technologies in the future."

This research was conducted with support from the Korea Brain Research Institute's institutional program under the Ministry of Science and ICT, the National Research Foundation of Korea, and the National IT Industry Promotion Agency (NIPA). The results were published in the latest issue of the international journal "Molecular & Cellular Proteomics (MCP)."

This content was produced with the assistance of AI translation services.