Greg Lemke, PhD, Salk Institute for Biological Studies, San Diego, CA, discusses microglial phagocytosis of plaques as a potential therapy for Alzheimer’s disease (AD). Plaques are similar to how macrophages behave in other tissues; when they have a threat they cannot defeat, they form a granuloma. A common example is in tuberculosis infections; macrophages form a granuloma around the bacteria via phagocytosis. The dense-core plaques of AD appear to be granulomas that have formed in the brain. The implication of this regarding therapy is that if it only targets the breaking of the dense-core plaques, it will be ineffective. Prof. Lemke further discusses how they are investigating the encouragement of microglial phagocytosis of the plaques. There have been PPAR-gamma activators known to ameliorate symptoms in amyloidogenic mouse models of AD – and this transcription factor upregulates the expression of the TAM receptors, Mer, in microglia. These drugs have been tried in clinical trials and have not been successful – however, there are many issues concerning the drug accessing the brain and accurately targeting the microglia. This interview took place at the AD/PD™ 2022 Conference in Barcelona, Spain.
