title: High Resolution Dissection of Reactive Glial Nets in Alzheimer's Disease.
abstract: Fixed human brain samples in tissue repositories hold great potential for unlocking complexities of the brain and its alteration with disease. However, current methodology for simultaneously resolving complex three-dimensional (3D) cellular anatomy and organization, as well as, intricate details of human brain cells in tissue has been limited due to weak labeling characteristics of the tissue and high background levels. To expose the potential of these samples, we developed a method to overcome these major limitations. This approach offers an unprecedented view of cytoarchitecture and subcellular detail of human brain cells, from cellular networks to individual synapses. Applying the method to AD samples, we expose complex features of microglial cells and astrocytes in the disease. Through this methodology, we show that these cells form specialized 3D structures in AD that we refer to as reactive glial nets (RGNs). RGNs are areas of concentrated neuronal injury, inflammation, and tauopathy and display unique features around β-amyloid plaque types. RGNs have conserved properties in an AD mouse model and display a developmental pattern coinciding with the progressive accumulation of neuropathology. The method provided here will help reveal novel features of the healthy and diseased human brain, and aid experimental design in translational brain research.
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada.
authors.forename: David S
authors.initials: DS
authors.lastname: Bouvier
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada.
authors.forename: Emma V
authors.initials: EV
authors.lastname: Jones
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada.
authors.forename: Gaël
authors.initials: G
authors.lastname: Quesseveur
authors.affiliation: Douglas Mental Health University Institute, Department of Psychiatry, McGill Group for Suicide Studies, McGill University, Montreal, Quebec, Canada.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Davoli
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada.
authors.forename: Tiago
authors.initials: T
authors.lastname: A Ferreira
authors.affiliation: Douglas Mental Health University Institute, Department of Psychiatry, McGill Group for Suicide Studies, McGill University, Montreal, Quebec, Canada.
authors.forename: Rémi
authors.initials: R
authors.lastname: Quirion
authors.affiliation: Douglas Mental Health University Institute, Department of Psychiatry, McGill Group for Suicide Studies, McGill University, Montreal, Quebec, Canada.
authors.forename: Naguib
authors.initials: N
authors.lastname: Mechawar
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada.
authors.forename: Keith K
authors.initials: KK
authors.lastname: Murai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000503:physiopathology*; D000818:Animals; D001253:Astrocytes / Q000473:pathology; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003933:Diagnosis; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D017628:Microglia / Q000473:pathology; D009457:Neuroglia / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000503:physiopathology*; D013569:Synapses / Q000473:pathology