Marmoset models of Alzheimer's disease will be developed, improved, maintained, and subjected to cognitive-behavioral, neuroimaging, physiological, biochemical, and pathological analyses using innovative technologies. Primate-specific phenotypes, pathophysiology, and neural circuit abnormalities will be elucidated through these analyses and utilized to develop new disease biomarkers and therapies. In addition, marmoset models of Rett syndrome will be constructed, maintained, and provided to other project researchers.

As experimental models of frontotemporal lobar degeneration (FTLD) or other neurodegenerative diseases, genetically modified marmosets will be developed, maintained, and analyzed for neuropathology and biochemical abnormalities. The role of a G protein–coupled receptor in FTLD pathology will be investigated. Using a marmoset disease model, the compounds that target this receptor will be examined to discover new therapies.

To support research on synucleinopathy, species-specific α-synuclein fibrils will be generated and provided. In addition, protocols for amplifying disease-specific α-synuclein fibrils will be developed, and amplified materials will be provided. Species- or disease-specific α-synuclein fibrils will be inoculated into the olfactory bulb or myenteric plexus to produce and supply animal models of synucleinopathy for research. Moreover, ultra-high-magnetic-field MRI and multi-channel electrocorticography measurements will be conducted in animal models of synucleinopathy, and methods for analyzing their pathological neural circuits will be developed and provided to researchers investigating these diseases.

We will establish a large-scale integrated database about neurodegenerative diseases. It will house data on aged individuals and patients with neurological disorders collected in the PADNI ( https://padni.org/ ) and other AMED programs such as Brain/MINDS and Brain/MINDS Beyond. This database will be consolidated by systematically linking to multimodal and multiscale datasets, such as normative statistics for large regional cohorts, biological markers, and postmortem human brain data. Furthermore, analytical pipelines for these systematically linked datasets will be created to support the development of disease diagnosis and prognosis models through machine learning. These results will assist with further research in the government, academic, and private sectors.

To develop and support neurodegenerative pathology technologies, a database that links ultrahigh spatial resolution MRI data with immunohistochemical (IHC) and mass spectrometry imaging (MSI) data will be launched. MRI measurements will include post-mortem healthy and neurodegenerative brains. These datasets will be used to train a deep-learning MRI model that describes or predicts various biological characteristics suggested by IHC and MSI measurements. These datasets will be applied to other research fields.

The IBISS installed at the NCNP's Integrative Brain Imaging Center serves as the data platform for the brain imaging cohort studies on neurological disorders conducted under the Brain/MINDS and Brain/MINDS Beyond programs. To facilitate the use of the collected data for further research, IBISS will be upgraded by installing and configuring data catalogs that enable enhanced search functionality and data visualization. IBISS will also provide the framework of data accumulation and storage capabilities for the subproject researchers conducting a new imaging research project.