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UCI Scientists Identify Underlying Contributor to Rare Neurodegenerative Disease

In a new study published in the journal Science Advances, University of California, Irvine researchers describe a new mechanism for the onset of a rare microgliopathy.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare autosomal dominant neurodegenerative disease associated with mutations of the Csf1r gene which is primarily expressed in microglia, the immune cell of the brain. As such, this gene has been a focus of neuroscientists who study ALSP. While the Csf1r gene is a prime candidate for study, the cellular mechanisms that link Csf1r to the onset of the disease remain unclear.

The UCI team, led by Neurobiology and Behavior Professor Kim Green, with graduate student Miguel Arreola, sought to identify the role that CSF1R and microglia play in the pathogenesis of ALSP. Using an inducible mouse model that restricts CSF1R loss to microglia, the team sought to determine how the loss of one Csf1r allele would impact brain homeostasis. The researchers discovered that the loss caused a disruption in microglial homeostasis accompanied by physiological changes similar to that found in human ALSP patients. The pathological changes were reversed after the restoration of homeostasis, or complete elimination, of dysfunctional microglia from the brains of the mice emphasizing how alterations in microglial phenotype can have a profound impact on the adult brain.

“These results show the dramatic impact that non-neuronal cells can have on brain function and disease, and likely involve common mechanisms across many neurodegenerative diseases, such as Alzheimer’s disease”

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