Basic Science and Pathogenesis

Area of Science:

• Neuroscience
• Biotechnology
• Stem Cell Biology

Background:

• Amyloid beta (Aβ) aggregation is central to Alzheimer's disease (AD) pathology, but its mechanisms are poorly understood due to limitations in current research models.
• Traditional 2D cultures and in vivo models fail to fully replicate human Aβ aggregation dynamics and neurotoxicity.
• 3D bioprinting offers a promising approach to create physiologically relevant human brain models using human induced pluripotent stem cells (hiPSCs) and biomaterials.

Purpose of the Study:

• To develop a 3D bioprinted human brain model capable of recapitulating amyloidogenesis.
• To investigate the formation and accumulation of amyloid beta plaques in a human-relevant in vitro system.
• To provide a novel platform for studying Alzheimer's disease mechanisms and facilitating drug discovery.

Main Methods:

• Development of a 3D bioprinted human brain model using iPSC-derived cortical neurons, astrocytes, and microglia in a multilayer structure.
• Incorporation of synthetic fibrillar Aβ42 (fAβ42) into the bioink to induce and study amyloid plaque formation.
• Long-term culture and analysis of Aβ aggregation dynamics and deposition within the 3D constructs.

Main Results:

• Statistically significant decrease in endogenous Aβ40 and Aβ42 levels in conditioned medium, indicating increased aggregation.
• Confirmation of increased Aβ deposit accumulation within the 3D-printed constructs via immunostaining (mOC87 and 4G8 positive).
• Successful long-term culture and observation of amyloidogenesis in a human-derived 3D brain model.

Conclusions:

• The 3D bioprinted human brain model effectively mimics amyloidogenesis, overcoming limitations of conventional in vitro models.
• This human-relevant platform enables real-time study of Aβ nucleation and plaque formation.
• The model serves as a novel tool for Alzheimer's disease research and drug discovery, reducing reliance on animal models.