Co-Pathological Connected Primary Neurons in a Microfluidic Device for Alzheimer Studies

This communication presents a novel experi- mental model for Alzheimer studies, where connected pri- mary neurons were set into subtend, co-pathological states. Cortical neurons were cultured in two separated cell com- partments in a microfluidic device. A neurite network was generated in a main channel through the neurite outgrowth from both cell compartments. A gradient of okadaic acid (OA) is generated over this neurite network by perfusion. OA is a phosphatase inhibitor that induces hyperphosphor- ylation of Tau proteins, a major hallmark in Alzheimer disease. The local OA treatment resulted in a connected ‘‘diseased’’ and ‘‘healthy’’ cell population. Anti-phosphory- lated tau (Ser262) staining confirmed different states of phosphorylated Tau proteins, and synapthophysin staining the connection of ‘‘healthy’’ and ‘‘diseased’’ cells. Here, we present a novel in vitro model that opens the possibility to study cellular and molecular propagation mechanisms in neurodegeneration, in Tauopathies (as e.g., in Alzheimer), as well as simultaneous drug effects on connected healthy and diseased cell populations.