Failure to detect tau in cortical dendritic spines by means of immunohistochemistry. Immunohistochemical labeling of hyperphosphorylated tau (antibodies AT8, AT100, and AT180) in cortical layer V pyramidal neurons (a-f) and hippocampal CA3 neurons (g-j). a-a” YFP-expressing neuron, filled with somatodendritic AT8-positive tau. The marked section of the apical dendrite (dashed rectangle in a”) is shown in higher magnification in b-b”, demonstrating that the protruding YFP-positive dendritic spines (exemplarily marked by arrowheads) are bare of hyperphosphorylated tau. c Example of a YFP-negative layer V neuron (c’-c”’, magnifications of the regions marked by dashed rectangles), containing AT8-positive tau in its soma, axon (arrows in c’), basal dendrites (arrowheads in c’), apical dendritic shaft (c”), and higher-order distal dendritic braches (arrowheads in c”’). An adjacent AT8-positive layer II/III neuron shows a similar punctate pattern of hyperphosphorylated tau in its dendritic filaments (arrows in c”’), not to be mistaken for emanating spines. AT8-labeling is also found irregularly in the neuropil, for example in neuritic dystrophies (asterisks in c”’). Different from the cortex, in hippocampal CA3 neurons, AT8-positive hyperphosphorylated tau was frequently found in spiny protrusions (inset in g, arrows). Images show maximum intensity projections. In c-j, images were inverted for contrast enhancement. Scale bars: 2 μm (b), 5 μm (c” & insets d, f &g), 10 μm (a, c’, c”’, e, h-j), 20 μm (c, d, f & g).