Immunohistochemical characterizations illustrating the lack of extracellular sortilin neuropathology in the human brain exhibiting primary age-related tauopathy (PART). The small whole brain map in (A) indicates that the sections were from the temporal lobe (TL) segment marked with a blue line (the same applies to other figures). Section orientation is indicated next to this map, with “M” toward medial and “S” toward superior in reference to anatomical position. Figure panel arrangement, neuroanatomical structures, cortical lamination, and scale bars are as indicated. Shown are TL sections immunolabeled for β-amyloid (Aβ) with the 6E10 monoclonal antibody (A), phosphorylated tau (pTau) with a polyclonal rabbit antibody (B), and sortilin with a rabbit antibody against the C-terminal (CT) domain (C). Enlarged views from the low-magnification images (A–C) are shown as inserts and panels as indicated (B,D–F). No extracellular Aβ deposition exists in the cortical regions and subregions of the hippocampal formation (A). Intensive pTau immunoreactivity (IR) is seen in hippocampus and transentorhinal areas, including CA1, prosubiculum (Pro-S), subiculum (Sub), presubiculum (Pre-S), and parasubiculum (Pare-S), whereas the IR is reduced as moving from the parahippocampal gyrus to the neocortical gyri (B). At high magnifications, pTau IR distinctly visualizes the somata and dendritic processes of a subset of pyramidal neurons in CA1 (insert in B) and Sub (D), whereas numerous fine neuronal processes are present in the background (D). In the neocortex, individual pyramidal-like neurons are visualized, with the IR filling up the somata and dendritic tree (E). Sortilin IR is exclusively cellular in the cortex and hippocampal formation (C), localizing to neuronal somata and dendritic processes (F). The regional distribution of pTau IR is consistent with a Braak stage III scoring of neurofibrillary tangle (NFT) pathology. Abbreviations: STG, MTG, and ITG: superior, middle, and inferior temporal gyri; FG: fusiform gyrus; DG: dentate gyrus; sts, its, and ots: superior, inferior, and occipitotemporal sulci; col-s: collateral sulcus; hf: hippocampal fissure; LV: lateral ventricle; WM: white matter; s.o.: strata oriens; s.p.: strata pyramidale; s.r.: strata radiatum; s.l.m.: stratum lacunosum-moleculare.