Fig. 4: Proteins involved in lipid transport are upregulated in PAASs.

a, GSEA was performed to compare PLD3-labeled proteins between humans with AD and unaffected controls. Pathway enrichment analysis was performed to cluster GSEA nodes. Each node represents a biological process or cellular component. The name of each cluster was curated based on the main GSEA biological processes and cellular components within each cluster. See also Supplementary Table 6. b, Detailed information on the lipid transport cluster. The biological process or cellular component of each node is listed. c, The eight top-ranked proteomic hits involved in the lipid transport cluster. The bar chart shows the FC and FDR of these hits by comparing PLD3-labeled humans with AD versus unaffected controls. d, Venn diagram showing that the eight top-ranked lipid transport–related proteins are shared between the human PAAS proteomes (821 proteins) and the AD upregulated proteins (98 proteins). A total of 75 proteins are shared between these two datasets. e,f, Representative zoomed-out (e) and zoomed-in (f) immunofluorescence confocal images of the top-ranked lipid-related proteomic hits in AD human brain, including C3, APOE, HDLBP, HEXB and TMEM30A. Scale bar, 5 μm. Zoomed-out images of all the proteins are shown in Extended Data Fig. 8. Quantification was performed in n = 3 AD human brains. Protein expression quantifications can be found in Supplementary Table 2. g, Representative immunofluorescence confocal images showing the anti-co-localized distribution of HDLBP (red) and the pan-axonal marker SMI312 (gray) within thickened axons in the AD human postmortem brain (n = 3). Scale bar, 5 μm. Ctrl, control.