Figure 1

Tau pathology in stratum pyramidale and stratum lucidum of area CA3 in sagittal sections from 13 ± 1 month old pro-aggregant Tau ^RDΔ mice. (a) Schematic drawing of a hippocampal mouse section containing the entorhinal cortex (EC). The drawing depicts the main hippocampal output region, the subiculum (SUB) followed by the cornu ammonis (CA) regions with areas CA1, CA3a, CA3b, and CA3c (hilus). The main input region from the EC to the hippocampus is the dentate gyrus (DG) containing the granule cells (red) which project to proximal apical dendrites of area CA3 principal cells (red). s.r. = stratum radiatum; s.l. = stratum lucidum; s.p. = stratum pyramidale. (b1-b3) Somatodendritic mislocalization of phosphorylated Tau (12E8 immunoreactivity) in pyramidal neurons (B3 red arrow) and 12E8-immunoreactivity of stratum lucidum (s.l.,b3, asterisk) of the CA3 region in 13 ± 1 month-old pro-aggregant mice (Pro). In contrast there is no 12E8 immunoreactivity in area CA3 of control littermates (Ctrl, b2). Magnification square from region (b3, white square) depicts 12E8 immunoreactivity in somata of pyramidal neurons (white arrows). (c1-c3) PHF1-Tau antibody detects Tau phosphorylation exclusively in stratum lucidum of pro-aggregant mice (Pro, c1). CA3 pyramidal cell bodies and their dendrites are spared (c3, white arrows). Control littermates show no PHF1 immunoreactivity (c2). A zoom-in of a region in C3 (white square) demonstrates that PHF-1immunoreactivity is found in s.l. with apical dendrites of CA3 pyramidal neurons are spared (white arrows). (d1-d3) Using Gallyas silver staining to monitor Tau aggregation we found aggregates predominantly in CA3a-c pyramidal neurons of s.p. (d1 and d3), whereas aggregation is absent in control littermates (d2). Representative images from at least three different mice per group showing consistent staining were selected.