a, Aβ and pTau pathologies in the CA1 and ERC. Both pathologies present wide distribution and intensity. Aβ pathology shows diffuse plaques with varied distribution and size (panels and insets). pTau pathology shows varied density of neurofibrillary tangles and diffuse Tau pathology. Scale bar, 500 μm. b, Neurons stained with Klüver–Barrera stain in the CA1 and ERC of the case with PSEN1-E280A/RELN-COLBOS, the case with PSEN1-E280A/APOECh, a case with average-onset PSEN1-E280A familial AD and a case with sporadic AD. Scale bar, 125 μm. c, Three-dimensional scatter plot for Aβ, pTau and neuronal density for ERC and CA1 from cases with RELN-COLBOS, APOECh, familial AD (n = 5) and sporadic AD (n = 4). The ERC in the case with RELN-COLBOS shows the highest neuronal density, with low Aβ and pTau pathologies. d, C-terminal RELN and APOE staining of the cases with RELN-COLBOS, APOECh, familial AD and sporadic AD in the ERC and CA1. The case with RELN-COLBOS shows a stronger background signal in both structures with lower intraneuronal signal for C-terminal RELN in the ERC. Similarly, the case with APOECh shows lower intraneuronal signal in ERC with the C-terminal RELN antibody and very low intraneuronal signal in both structures with the APOE antibody (magnified right). Finally, APOE staining shows noticeable plaque- and tangle-like signals in cases with familial and sporadic AD in both structures, the ERC and CA1. Scale bars, 100 μm and 25 μm in the magnified panel. e, Klüver–Barrera staining of whole hippocampal and parahippocampal sections (top), together with representative magnified images of parahippocampal subcortical white matter stained with C-terminal RELN antibody in the cases with RELN-COLBOS, APOECh, familial and sporadic AD (bottom). The case with RELN-COLBOS showed increased white matter Luxol Fast Blue signal intensity, while the cases with RELN-COLBOS and sporadic AD showed increased intracellular C-terminal RELN signal in white matter. Scale bars, 2.5 mm for the top panel and 25 μm for the bottom panel.