Accumulation of Vesicle-Associated Human Tau in Distal Dendrites Drives Degeneration and Tau Secretion in an In Situ Cellular Tauopathy Model
The intracellular distribution of exogenous human tau versus controls. (a) Somatodendritic sections through ABCs expressing tau (top) and an expression control GFP (bottom) showing the selective axonal (asterisk) and distal dendritic distribution (arrows) of tau versus the relatively even distribution of exogenous protein. (b) Tau immunolabel is somewhat more concentrated in the proximal axon than in proximal dendrites in low expressing ABCs. However, any selective localization to the axon (asterisk) is slight and appears to be lost entirely when normalized to MT immunolabel. (c) Examples of double-labeled sections through the somata and dendrites of ABCs exhibiting low (left) and high (left center) tau expression illustrate the characteristic changes in tau distribution with expression level and their relationship with dendritic beading and MT distribution relative to NF-180 expression controls. Tau (red) and tubulin (green) are colocalized in the proximal dendrites of low expressing cells (asterisk), but tau immunolabel becomes significantly more distally located than that of tubulin in ABCs expressing higher tau levels (right, double asterisks). Note that the expression controls do not affect MT distribution when NF-180 is expressed in ABCs (right panels). (d) Human tau expression appear to “bundle” endogenous MTs (compare green channel label at arrows), even when tau expression is above MT saturation, unlike the situation with dendrites. Scale bars: 50 μm.
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