Lead author Neta Rosenzweig, PhD, of the Ann Romney Center for Neurological Diseases, and senior author Oleg Butovsky, PhD, of the Ann Romney Center and Gene Lay Institute of Immunology and Inflammation, share key messages from their paper "Sex-Dependent APOE4 Neutrophil-Microglia Interactions Drive Cognitive Impairment in Alzheimer's Disease" published in Nature Medicine. How would you summarize your study for a lay audience? In this manuscript, we identify that a major genetic risk factor for the late onset of Alzheimer's disease, APOE4, impairs the communication of immune cell neutrophils with immune cells of the brain microglia. This miscommunication leads to cognitive impairment in female Alzheimer's patients.
One of the mechanisms identified was related to the induced expression of an immune molecule called IL17F in neutrophils, which causes microglia not to respond to neurodegeneration. Our findings from blocking this molecule in preclinical models of Alzheimer's disease suggests a potential translational basis for unmet clinical needs. What question were you investigating? We asked how sex, APOE4, and cognitive status interact in regulating neutrophil phenotype and functions that impair microglial response to neurodegeneration.
We also asked whether APOE4 regulates neutrophils in a cell-autonomous manner and whether deleting APOE4 in neutrophils could affect microglial phenotype and AD pathology in mouse models. What methods or approach did you use? In collaboration w.
