Article Figures & Data
Figures
- Figure 1.
Cortical surface views of the ALE meta-analysis results. Regions where hypometabolism was not detected are transparent (ALE value of 0.006 or less). Lower glucose utilization (AD vs controls) ranges from low (yellow) to high (black).
- Figure 2.
SRP-dependent cotranslational genes ranked based on differential expression in hypometabolic regions associated with AD. Genes are marked with dots, with the y-axis representing the genome-wide differential expression rank and ranges from overexpression (top) to underexpression (bottom). The black line marks the median expression rank of the SRP-dependent cotranslational genes. The dashed gray line marks the gene with the most stable expression between inside and outside of each donor’s hypometabolic regions. Red highlights genes that pass correction for multiple testing.
- Figure 3.
Heatmap of the ER translocation gene expression across three microglia cell clusters from the AD mouse model (left half) and AD pathology subgroups (right half). Expression for each gene is z-scored with high expression in red and low in blue. Genes are ordered based on hierarchical clustering using complete linkage (genes with similar expression across the mouse and human data are clustered together). Three human genes are duplicated because they have two homologous mouse genes (RPL6, RPL13, and SRP54). Human genes without homologous mouse genes are not displayed. Complete results spanning all GO groups are available as Extended Data Figure 3-1 (AD mouse model) and Extended Data Figure 3-2 (AD pathology subgroups). Data from other cell types in the AD pathology subgroups for the ER translocation genes are available in Extended Data Figure 3-3.
Tables
- Table 1
Top GO groups enriched for differential expression in areas of AD-associated hypometabolism in brain 10 021/H0351.2002
Name Genes ID AUC p valueFDR SRP-dependent cotranslational protein targeting to membrane 87 GO:0006614 0.874 1.35E-29 Cotranslational protein targeting to membrane 90 GO:0006613 0.865 2.07E-29 Protein targeting to ER 92 GO:0045047 0.847 2.86E-27 Cytosolic ribosome 87 GO:0022626 0.856 3.45E-27 Establishment of protein localization to endoplasmic reticulum 96 GO:0072599 0.828 1.66E-25 Structural constituent of ribosome 107 GO:0003735 0.794 1.05E-22 Ribosomal subunit 158 GO:0044391 0.737 1.01E-21 Nuclear-transcribed mRNA catabolic process, nonsense-mediated decay 104 GO:0000184 0.783 2.07E-20 Protein localization to endoplasmic reticulum 109 GO:0070972 0.765 9.44E-19 Cytosolic large ribosomal subunit 47 GO:0022625 0.894 6.73E-18 microtubule organizing center part 145 GO:0044450 0.395 0.00244 DNA-dependent ATPase activity 59 GO:0008094 0.33 0.00145 HOPS complex 13 GO:0030897 0.137 0.00135 ATPase activity, coupled 186 GO:0042623 0.396 0.00026 tRNA aminoacylation for protein translation 40 GO:0006418 0.268 9.84E-05 Amino acid activation 43 GO:0043038 0.275 8.24E-05 Aminoacyl-tRNA ligase activity 33 GO:0004812 0.243 8.24E-05 Cullin-RING ubiquitin ligase complex 111 GO:0031461 0.355 3.84E-05 tRNA aminoacylation 42 GO:0043039 0.259 1.91E-05 Ubiquitin ligase complex 195 GO:0000151 0.368 7.35E-08
Extended Data 1
Zip file containing Rand Python source code to reproduce the analyses. Download Extended Data 1, ZIP file.
Figure 1-1
Details of the FDG-PET studies used in the meta-analysis. Download Figure 1-1, XLSX file.
Table 1-1
Complete GO enrichment results for all donors separately. Download Table 1-1, XLS file.
Figure 3-1
Complete GO enrichment results for step-wise increases across DAM clusters. Download Figure 3-1, CSV file.
Figure 3-2
Complete GO enrichment results for step-wise increases across the human AD pathology subgroups. Download Figure 3-2, CSV file.
Figure 3-3
ER translocation gene step-wise results for other cell-types across the human AD pathology subgroups. Download Figure 3-3, CSV file.
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