Molecular Horizons Seminar - Dr Molly Swanson

Mi croglia, the innate immune cells of the brain, become reactive (with altered functions) in response to damage or disease. Significant evidence now suggests changes in microglial function contribute to disease pathogenesis, including in Alzheimer’s disease (AD) and motor neuron disease (MND). Previous studies had identified microglial changes in AD and MND post-mortem human brain tissue, but these studies were limited by using single chromogen labelling or tissue-wide analyses that did not capture microglial heterogeneity. A more comprehensive analysis of microglial changes relative to disease-specific pathological proteins in the human brain was necessary to identify disease-specific microglial phenotypes. This presentation will highlight some of the unique microglial changes identified in post-mortem human tissue from AD and MND patients (Neurological Foundation Human Brain Bank, Centre for Brain Research). Multiplexed immunohistochemistry has allowed for the co-labelling of up to 20 markers in a single tissue section. This, in conjunction with novel single-cell image analysis pipelines, allows for an in-depth interrogation of microglial changes relative to disease-specific pathology. Collectively, this work has identified unique microglial phenotypes emerging in the diseased human brain which is key to determining how microglia should be targeted therapeutically to slow disease progression.