Development of fast-forming 3D cultures of human neurons for modeling Alzheimers disease amyloid and Tau pathology

Research Project

Project/Area Number	20K07771
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 51030:Pathophysiologic neuroscience-related
Research Institution	Okinawa Institute of Science and Technology Graduate University
Principal Investigator	Dimitrov Dimitar 沖縄科学技術大学院大学, 細胞分子シナプス機能ユニット, 技術員 (70568865)
Project Period (FY)	2020-04-01 – 2023-03-31
Project Status	Completed (Fiscal Year 2022)
Budget Amount *help	¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000) Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	Alzheimer's disease / Neurodome / 3D culture / amyloind plaques / neurofibrialy tangles / tau aggregates / tau phosphorylation / amyloid beta / Alzheimer's model / Tau pathology / Neurodome culture / semi-3D culture / iPSC-neurons / Alzheimer's Disease / Neurodegeneration model / Tauopathy model / amyloid plaques / Disease model / 3D neuron culture / neurodome / amyloid plaque / neurofibliary tangles
Outline of Research at the Start	Alzheimer’s disease (AD) is a devastating and fatal form of neurodegeneration, with no cure.This project aims to develop a culture model, called 'Neurodome', where human neurons are cultured in a semi-3D formation and develop AD main pathology, and will aid in studying AD and develop treatment.
Outline of Final Research Achievements	Alzheimer’s disease (AD) pathology presents as extracellular accumulation of beta-amyloid (Aβ) peptides (Aβ plaques), intracellular hyperphosphorylated tau aggregates (neurofibrillary tangles), and subsequently loss of synapses leading to progressive cognitive decline and neuronal cell death. Despite extensive effort, and many drugs tested worldwide, there is not successful drug that can stop the progression of the disease. One reason for that is that there are no good disease in vitro or animal models that can reproduce the disease pathology and progression. Thus it is necessary to develop better in vitro models for AD, in order to develop successful treatment strategies. This research describes a semi-3D neuronal culture named "neurodome" culture, that shows better pathology of AD such as plaques accompanied by tau tangles.
Academic Significance and Societal Importance of the Research Achievements	The interest for developing adequate in vitro models　is huge. The neurodome is easy and fast to culture, and mimics well the main hallmarks of AD.　This help with advances in disease understanding, better evaluation of therapeutic interventions, reduced use of animal models, personalized approaches.