For decades, neurons were the focus of Alzheimer’s research. After all, they die off in large numbers over the course of the disease and are considered the primary cells for memory and other cognitive brain activity. However, when large-scale genetic sequencing of Alzheimer’s patients became possible, the field discovered that the genetics of neurons are not common risk factors for most cases of Alzheimer’s.
Of the common genes with variants that affect risk of sporadic Alzheimer’s disease, more than half are made by microglia, astrocytes and peripheral myeloid cells—not neurons. These cells are the primary immune cells of the central nervous system, and they continuously monitor the brain, quickly responding to pathological changes. They play a crucial role in maintaining brain homeostasis by isolating and clearing out cell debris, pathogens, and cellular byproducts, including amyloid beta plaques. However, under certain conditions, these immune cells can start to malfunction, even degrading healthy synapses and neurons. This is thought to contribute to the neurodegeneration and cognitive decline observed in Alzheimer’s disease.
Neuroinflammation has long been recognized as a hallmark of Alzheimer’s disease, dating back to Dr. Alois Alzheimer’s observations of reactive glial cells in the brain. Modern research suggests that this inflammatory response plays a more active role in disease progression than previously thought. The researchers within the neuroimmune consortium already have identified several genes in microglia important for the development of Alzheimer’s-related pathologies, and demonstrated how these genetic changes can influence peripheral signaling, such as cytokine and hormone responses. Now, the consortium is investigating how inflammation outside the brain may directly impact Alzheimer’s pathology. This bidirectional communication between the brain and the body is crucial for maintaining normal brain function and, when disrupted, may contribute to both the onset and progression of Alzheimer’s disease.
The consortium includes experienced investigators with a track record of collaboration and highly complementary expertise across methods, species, cell types, and in brain and peripheral systems.
NEUROIMMUNE CONSORTIUM: FUNDED RESEARCHERS
Mathew Blurton-Jones, Ph.D., University of California, Irvine
Christopher K. Glass, M.D., Ph.D., University of California, San Diego
Shane Liddelow, Ph.D., New York University Langone Health
Beth Stevens, Ph.D., Boston Children’s Hospital; Chair, CureAlz Neuroimmune Consortium
Martine Therrien, Ph.D., University of California, Davis
Read The Neuroimmune System And Alzheimer’s Disease Brochure here