Fig. 3

ApoER2 expression parallels regional, laminar, and cellular vulnerabilities to NFT pathology. Panels A–D are coronal sections of the ErC (A), ProS-CA1 border region (B), middle temporal gyrus (C), and transverse sections of the upper pons (D) from one representative middle-aged Braak stage I non-AD control. Soma and neuritic projections are demarcated by arrows and open arrows, respectively. Composite MP-IHC images were used to provide cytoarchitectural and pathological context for single-marker IHC images. ErC (A_1–10): LRP8 gene (LRP8_M) (A_1–5) and ApoER2 protein (A_6–10) are strongly expressed by stellate-shaped Reelin-expressing (RELN) neurons in (A_1–2,7–8), a subset of L2 pyramids (A_3–4), and basal and apical dendritic tufts emanating from L2 neurons (A_7–9). A visible laminar threshold (broken arrows in A_6–8) for ApoER2 expression was observed near the L2–L3 border (A₁₀); p value based on Wilcoxon rank-sum test. LRP8 and ApoER2 are strongly expressed by a subset of L4 pyramids and surrounding neurites (A₅, A₉); adjacent L4 neurons with low ApoER2 expression are demarcated by an * in A₉. ProS-CA1 region (B_1–10): Strong LRP8 (B_1–5) and ApoER2 (B_6–10) expression was observed in a subset of basal pyramids (B_1–2) and neurons localized to the basal stripe (B_4–5). Pyramids located in the middle and apical laminae tended to have lower LRP8 and ApoER2 expression (B₃). Temporal neocortex (C_1–5): Strong ApoER2 expression in a subset of neocortical L3 and L5 pyramids, apical and basal dendritic projections (C_3–4), and highly-ramified apical dendritic tufts (C₁) located in the vicinity of L2. ApoER2 expression was low or absent in neighboring L3 pyramids (demarcated by * in C₂) and most L4 stellate-shaped neurons (C₃). A visible laminar threshold (broken arrow in C₁) was observed near the L2–L3 border (C₅); p value based on Wilcoxon rank-sum test. Pontine LC and raphe nucleus (D_1–10): Strong ApoER2 protein (D_1–2,6–8) and LRP8 gene (LRP8_M and LRP8_L) (D_3–5,9–10) expression was observed in fusiform-shaped and multipolar LC neurons (D_2–5) and in their MAP2-labeled dendritic tufts emanating into the peri-coeruleus region (oval in D_2, white arrows in D_4–5). ApoER2 (D_6–8) and LRP8 (D_9–10) are also strongly expressed in neurons and neuritic projections in the raphe nucleus. Scale bars in MP-IHC images = 5µm.