O3‐10‐05: ROBUST MOLECULAR PROPERTIES UNDERLYING REGIONAL VULNERABILITY TO AMYLOID DEPOSITION AND NEURODEGENERATION IN ALZHEIMER'S DISEASE

• DOI: 10.1016/j.jalz.2018.06.2829
• Publication Date: 2018-10-22T10:20:22Z
• Authors: Irina Jelistratova; Jorge Sepulcre; Gabriel González-...; Stefan J. Teipel; Michel J. Grothe
• Keywords: Human brain

In previous research we have identified distinct molecular properties underlying regional vulnerability to amyloid deposition and neurodegeneration in AD by studying the respective neuroimaging patterns relation transcriptional architecture of human brain, as determined median gene expression profiles across six brain donors contributing Allen Human Brain Atlas (AHBA). Given that differ individual donors, here examined robustness imaging-genetic associations donor profiles. The brain-wide AD-typical were estimated contrasting Florbetapir-PET high-resolution structural MRI data, respectively, between biomarker-confirmed groups 75 patients 126 healthy controls participating ADNI study. For each AHBA microarray measurements genome-wide mapped into Desikan-Killiany anatomical atlas further summarized one combined (median) transcriptome profile. Regional levels degree AD-related pathology assessed using spatial correlation analysis for APP MAPT genes interest, well Gene Set Enrichment Analysis (GSEA) identification differentially expressed functional sets. Imaging-genetic profile their Initially correlations deposition, displayed large variations analyses (Fig.1). By contrast, over a half sets GSEA be underexpressed amyloid-vulnerable regions (Table 1), overexpressed neurodegeneration-vulnerable 2), could replicated at least 2/3 These included related major biochemical pathways "protein synthesis" "mitochondrial respiration" those "cellular differentiation neurite formation" "extracellular signal-regulated (MAPK/ERK) kinase pathways" neurodegeneration. a) Associations AD-topical neurodegeneraticn -with genes. severities (top) (bottom) are plotted against (left) (right) 32 covering entire cerebral cortex. Linear trends indicated regression lines ρ indicates Spearman coefficient. Green/red colours indicate statistical significance non-significance threshold p < 0.05. (Figure adapted from Grothe et al., 2018) b) Identified (r=0.44. p=0.012), (r=0.46. p=0.008) meet only 1 2 respectively. Individual same order both displays. highlights <0.05. may primarily reflecting specific classes pathways, rather than single precursor proteins (APP) tau (MAPT) pathology.