Extended Data Fig. 6: SMOC1 characterization in postmortem human tissue.

a, Differential gene expression for SMOC1 (strongest protein associated with Aβ) across all cell types and with five measures of AD pathology was accessed from Mathys et al, Cell, 2023, based on single-nuclei data from 427 ROSMAP donors. Only associations (two-sided regressions) surviving correction for false discovery rate across all cell types are depicted. Amyloid plaque and tau tangle loads were quantified with immunohistochemistry (IHC) (AT8 antibody for tau) and averaged across 8 brain regions. Diffuse plaques, neuritic places and neurofibrillary were assessed with silver-stained slides in 5 brain regions. Overall there were higher SMOC1 levels with greater postmortem AD pathology predominantly in OPCs, and to some extent in astrocytes and some inhibitory neuronal subtypes, reflecting the cell types where this gene is mainly expressed. b,c Representative images of entorhinal cortex from a nondemented control (NC) (b) and an Alzheimer’s disease (AD) (c) patient stained against SMOC1 (red) and the nuclei marker DAPI (blue). d, Optical density (OD) area fraction of SMOC1 in entorhinal cortex in six NC and six AD patients. Each point represents the mean of the OD area fraction in six images captured from each case. The data was analyzed using 2-sided student t-test. Significant difference at ***p < 0.001. e-g, Example of double staining against SMOC1 (red) and Methoxy-04 staining plaques (blue). e, SMOC1 staining. f, Aβ plaques staining. g, Merged image of SMOC1 and plaques. SMOC1 were found in some (long arrow), but not all (short arrow) Methoxy-04 stained plaques, which were found in three out of six AD cases. Overall, we found higher SMOC1 levels in brain tissue from AD cases compared to controls, with SMOC1 localized in amyloid plaques. Scale bar in (b-c) = 10 μm and in (g) = 50μm.