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Call it Mighty Mouse: Breakthrough leaps Alzheimer’s research hurdle

UCI-led study reveals crucial mechanisms contributing to the disease

University of California, Irvine researchers have made it possible to learn how key human brain cells respond to Alzheimer’s, vaulting a major obstacle in the quest to understand and one day vanquish it. By developing a way for human brain immune cells known as microglia to grow and function in mice, scientists now have an unprecedented view of crucial mechanisms contributing to the disease.

The team, led by Mathew Blurton-Jones, associate professor of neurobiology & behavior, said the breakthrough also holds promise for investigating many other neurological conditions such as Parkinson’s, traumatic brain injury, and stroke. The details of their study have just been published in the journal Neuron. Link to study: https://www.cell.com/neuron/fulltext/S0896-6273(19)30600-2.

To read the full article, click Here.

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Hasselmann and Coburn et al. publish in Neuron

Development of a Chimeric Model to Study and Manipulate Human Microglia In Vivo

iPSC-derived microglia offer a powerful tool to study microglial homeostasis and disease-associated inflammatory responses. Yet, microglia are highly sensitive to their environment, exhibiting transcriptomic deficiencies when kept in isolation from the brain. Furthermore, species-specific genetic variations demonstrate that rodent microglia fail to fully recapitulate the human condition. To address this, we developed an approach to study human microglia within a surrogate brain environment. Transplantation of iPSC-derived hematopoietic-progenitors into the postnatal brain of humanized, immune-deficient mice results in context-dependent differentiation into microglia and other CNS macrophages, acquisition of an ex vivo human microglial gene signature, and responsiveness to both acute and chronic insults. Most notably, transplanted microglia exhibit robust transcriptional responses to Aβ-plaques that only partially overlap with that of murine microglia, revealing new, human-specific Aβ-responsive genes. We therefore have demonstrated that this chimeric model provides a powerful new system to examine the in vivo function of patient-derived and genetically modified microglia.