AUTHOR=Mezias Chris , Raj Ashish TITLE=Analysis of Amyloid-β Pathology Spread in Mouse Models Suggests Spread Is Driven by Spatial Proximity, Not Connectivity JOURNAL=Frontiers in Neurology VOLUME=Volume 8 - 2017 YEAR=2017 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2017.00653 DOI=10.3389/fneur.2017.00653 ISSN=1664-2295 ABSTRACT=

While the spread of some neurodegenerative disease-associated proteinopathies, such as tau and α-synuclein, is well studied and clearly implicates transsynaptic pathology transmission, research into the progressive spread of amyloid-β pathology has been less clear. In fact, prior analyses of transregional amyloid-β pathology spread have implicated both transsynaptic and other intracellular- as well as extracellular-based transmission mechanisms. We therefore conducted the current meta-analytic analysis to help assess whether spatiotemporal amyloid-β pathology development patterns in mouse models, where regional proteinopathy is more directly characterizable than in patients, better fit with transsynaptic- or extracellular-based theories of pathology spread. We find that, consistently across the datasets used in this study, spatiotemporal amyloid-β pathology patterns are more consistent with extracellular-based explanations of pathology spread. Furthermore, we find that regional levels of amyloid precursor protein in a mouse model are also better correlated with expected pathology patterns based on extracellular, rather than intracellular or transsynaptic spread.