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ARUK 2022 | Aberrant synapse ingestion by microglia and astrocytes in Alzheimer’s disease

Makis Tzioras, PhD, The University of Edinburgh, Edinburgh, UK, shares the details of a study which has revealed altered synaptic ingestion by human microglia and astrocytes in the brains of individuals with Alzheimer’s disease. Confocal microscopy and immunohistochemistry were used to label and visualize specific markers of synapses and glia in human postmortem brain tissue samples, which showed that microglia and astrocytes from Alzheimer’s brains contained greater amounts of synaptic proteins, compared to non-diseased brain tissue. Additionally, Dr Tzioras and colleagues demonstrated that Alzheimer’s brain derived synapses are phagocytosed more readily than controls by insolated human glial cells. These findings implicate aberrant synapse ingestion by glial cells in disease pathobiology. Ongoing work to elucidate what is changing in these synapse to cause their untimely ingestion by glia has implicated MFGE8 in the process, a secreted protein which binds to cell surface molecules to mediate engulfment. This interview took place at the Alzheimer’s Research UK Conference 2022 in Brighton, UK.