Fig. 1

Light microscopic images showing the distribution of sortilin immunolabeling across the brain of a 2-month-old five familial Alzheimer’s disease mutations transgenic (5×FAD) mouse with transgenic background confirmation. a, c, and e Low-magnification images of adjacent parasagittal sections immunohistochemically stained with the rabbit sortilin antibody raised against the intracellular C-terminal domain, as well as with the monoclonal β-amyloid (Aβ) antibody 6E10 and the PHF1 mouse anti-phosphorylated tau (p-tau) antibody, for transgenic phenotype validation. Neocortical and subicular areas (boxes) are enlarged and shown in other panels as indicated. Sortilin immunolabeling occurs in the somata and proximal dendrites of cortical and hippocampal neurons (a, b, g), denser in those of relatively large somal size representing likely pyramidal neurons (b, g). The 6E10 antibody, which can recognize transgenic human β-amyloid precursor protein (hAPP) as well as Aβ, heavily labels cells in the middle portion of the cerebral cortex and stratum pyramidale (s.p.) of the hippocampus and subiculum (b, d, h). The heavy 6E10 immunoreactivity in layer V (d) and subicular (h) pyramidal neurons represents strong expression of transgenic hAPP in these neurons. Two extracellular miniplaques (arrows) are visible at the stratum oriens (s.o.) of the subiculum (h, i). The PHF1 antibody reveals background reactivity without any distinct cellular immunolabeling across the entire brain (e, f, j). OB Olfactory bulb, FC Frontal cortex, PC Parietal cortex, OC Occipital cortex, Sept Septum, LV Lateral ventricle, CA1 CA1 subsector of the hippocampus, DG Dentate gyrus, Th Thalamus, SC Superior colliculus, IC Inferior colliculus, MB Midbrain, MO Medulla oblongata. Scale bar = 1 mm in (a) applying to (c, e), equivalent to 100 μm for (b–h, j) and 25 μm for (i)