Accumulation of Vesicle-Associated Human Tau in Distal Dendrites Drives Degeneration and Tau Secretion in an In Situ Cellular Tauopathy Model
Exogenous tau expression can redistribute and sequester endogenous cytoskeletal elements. (a) Expression of exogenous human tau in ABCs at moderate expression levels can result in the colocalization of tau with endogenous NFs where tau accumulates in dendritic tips. Note that NF immunolabel in nonexpressing ABCs decreases to neuropil levels in the distal dendrites and that aggregates of NF immunolabel occur only with tau co-localization. The locations of large proximal (1) and smaller distal dendrites (2, 3) are indicated. (b) (1) top: NF distribution in a large dendrite of an ABC expressing tau at moderate levels is independent of tau (red channel). (2) bottom: significant changes in NF distribution in more distal dendrites (location 2 in (a)), with extensive overlap between the red (tau) and green (NF) channels and relocalization of NFs into punctate deposits (carets) that accumulate in dendritic beads (arrow). (c) shows tau (red) and fluorescently tagged phalloidin (filamentous actin, green) distribution. Colocalized voxels can be found in distal dendrites (blue channel). (d) shows high magnification views of co-localized tau (red channel) with NF protein (top), with tubulin (bottom, green channel), and f-actin (bottom, blue channel) in amorphous aggregates (asterisks) at the distal tips of the ABC shown in (3). Note that the white aggregates shown in the bottom image (asterisks) are the result of colocalization of tau with both tubulin (DM1A) and f-actin (phalloidin). Scale bars: (a) 50 μm, (b) 10 μm, (c) 20 μm, (d) 5 μm.
Article of the Year Award: Outstanding research contributions of 2020, as selected by our Chief Editors. Read the winning articles.