High Resolution Dissection of Reactive Glial Nets in Alzheimer's Disease.

TitleHigh Resolution Dissection of Reactive Glial Nets in Alzheimer's Disease.
Publication TypeJournal Article
Year of Publication2016
AuthorsBouvier DS, Jones EV, Quesseveur G, Davoli MAntonietta, Ferreira TA, Quirion R, Mechawar N, Murai KK
JournalSci Rep
Volume6
Pagination24544
Date Published2016 Apr 19
ISSN2045-2322
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.

DOI10.1038/srep24544
Alternate JournalSci Rep
PubMed ID27090093
PubMed Central IDPMC4835751
Grant List / / Canadian Institutes of Health Research / Canada