Co-pathological connected primary neurons in a microfluidic device for Alzheimer studies.

Area of Science:

• Neuroscience
• Cell Biology
• Biomedical Engineering

Background:

• Alzheimer disease is characterized by Tau protein hyperphosphorylation.
• Current in vitro models often lack the complexity to study disease propagation between connected neuronal populations.
• Investigating cellular mechanisms of neurodegeneration requires sophisticated experimental systems.

Discussion:

• A novel microfluidic device enables the culture of primary cortical neurons in separated compartments.
• A neurite network connects these compartments, allowing for intercellular communication.
• Okadaic acid (OA) perfusion creates a localized gradient, inducing Tau hyperphosphorylation in a subset of neurons.

Key Insights:

• This model successfully establishes co-pathological states within connected neuronal networks.
• Distinct phosphorylation states of Tau protein (p-Tau) were confirmed using anti-phosphorylated tau (Ser262) staining.
• Synaptophysin staining verified the functional connectivity between healthy and diseased neuronal populations.

Outlook:

• This model provides a platform for studying the propagation of Tau pathology in Alzheimer disease and other tauopathies.
• It facilitates the investigation of simultaneous drug effects on both healthy and diseased neuronal populations.
• Future research can explore intercellular signaling and therapeutic interventions in a more physiologically relevant in vitro setting.