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Alzheimer's, microglia and immune cells

iPSC derived models

The complexity of Alzheimer’s disease

Despite over 40 years of intense research efforts no effective treatment for Alzheimer’s disease (AD) exists. Alois Alzheimer first described the histopathology of AD which is characterized by brain atrophy, amyloid plaques neurofibrillary tangles loss of neurons and synapses, and dystrophic neurites. In addition, Alzheimer noted, “The glia have developed numerous fibers”. The proliferation and activation of microglia in the brain, concentrated around amyloid plaques, is a prominent feature of of the disease and of increasing interest in drug discovery.

Microglia cells are the immune cells of the central nervous system and consequently play important roles in infections and inflammation. In the brain, microglia are highly dynamic, moving constantly to actively survey the brain parenchyma. There is abundant evidence that activated microglia can be harmful to neurons.

Co-culture, using human iPSC derived neurons, astrocytes and microglia is already providing a new platform for disease modelling of neurodegenerative diseases and for the investigation of potential treatments for these conditions.

High throughput co-culture screening

Scientists from Genentech and UCSF have created a high-throughput screening model of AD by co-culturing large numbers (100-200 million) of human iPSC-derived neurons, astrocytes and microglia in 384 well plates in an automated fashion over a long period of time. Their study showed that long-term, automated co-culture of iPSC cells to create a model of neurodegenerative disease is possible and successfully recapitulates the hallmarks of human AD pathology.

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