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David Bouvier, Luis Salamanca, Rudi Balling and Alexander Skupin. (Luxembourg Centre of Systems Biomedicine, University of Luxembourg, Belval, Luxembourg)The hippocampus, the “memory center” of the brain, is one of the brain regions the most severely affected by Alzheimer’s Disease (AD) where early neuronal loss lead to severe memory impairments. However the cellular mechanisms behind the death of hippocampal neurons in AD still need to be deciphered. We have used an improved immunohistochemical method that allows multi-channel, high-resolution 3D light microscopic analysis on thick fixed post-mortem samples of human brains. This method provides simultaneous resolution of 3D relationships between neurons and glial cells across large tissue landscapes of AD brain tissue. We were able to explore the hippocampus and unveil an extreme cellular event: the complete engulfment of a damaged CA1 pyramidal neuron by a macro-cluster of voracious microglia. Applying our developed segmentation method to 3D high-resolution images allows for quantifying the process of microglia eating neurons leading to impairment of the memory network in late stages of AD. This shows how our approach offers a new view on the cyto-architecture and subcellular details of human brain cells and improves our understanding of the cellular alterations