Summary of the project

As a major societal challenge associated with population aging, dementia and related disorders are increasing worldwide. Recent studies have revealed that systemic abnormalities, including autonomic dysfunction, gastrointestinal dysfunction, sensory impairment, diabetes, and systemic inflammation, are present at the earliest stages of these diseases. Our project aims to elucidate the causal relationships between alterations in inter-organ networks and the onset of dementia-related disorders. By 2050, through integration with the outcomes of other Goal 2 projects, we aim to realize ultra-early disease prediction and prevention technologies based on a whole-body network simulator. To achieve this vision, we will elucidate dementia-related inter-organ networks by 2030 and establish ultra-early disease prediction.
During the first five years, our research framework was organized around the major types of dementia. In the second half of the project, we reorganized it to view dementia as disorders characterized by the accumulation of abnormal protein aggregates in the brain. Our research focuses on (1) mechanisms of protein aggregate formation and propagation, (2) mechanisms of protein aggregate clearance, (3) central and peripheral immune pathophysiology, (4) behavioral, physiological, and imaging biomarkers, and (5) bio-mathematical integration as a cross-cutting theme. Together, these efforts will advance our understanding of disease mechanisms and contribute to ultra-early prediction and prevention of dementia by 2050.

Milestone by year 2030

• lucidation of inter-organ networks enabling ultra-early prediction and prevention of dementia.
• Proof-of-concept studies of preventive strategies in animal models and preparation for clinical translation.

R&D Items through FY2025

• [1-4] Brain and multi-organ network in Alzheimer’s disease, vascular dementia and Parkinson’s disease dementia (1)
• [1-4] Brain and multi-organ network in Alzheimer’s disease, vascular dementia and Parkinson’s disease dementia (2)
• [5] Elucidation of Inter-Organ Networks in Dementias by AI and Mathematical Research
• Progress Report (474KB)

R&D Items from FY2026

• [101] Establishment of a biological diagnosis of Parkinson’s disease using biofluid biomarkers of protein aggregates
• [102] Realization of ultra-early diagnosis through the development of PET probes for protein aggregates and blood-based biomarkers
• [103] Development of Parkinson’s disease biomarkers and therapeutics using model mice and prodromal and post-diagnosis cohorts
• [104] Elucidation of inter-organ networks in vascular and mixed dementia focusing on the neurovascular unit–lymphatic system, and development of risk prediction methods through clinical translation
• [105] Elucidation of inter-organ networks in Alzheimer’s disease focusing on brain–peripheral organ interactions, and development of risk prediction methods through clinical translation
• [111] Elucidation of mechanisms of protein aggregate formation and propagation in dementia
• [112] Elucidation of mechanisms of protein aggregate clearance and processing in dementia
• [113] ​Elucidation of central and peripheral immune pathophysiology in dementia
• [114] ​Development of multimodal biomarkers for dementia
• [115] Interdisciplinary integration of biological and mathematical approaches in dementia
• [116] Ethical, Legal, and Social Issues (ELSI) research in dementia

Performers

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• Summary of the project (267 KB)