A Genome-wide Gene-Expression Analysis and Database in Transgenic Mice during Development of Amyloid or Tau Pathology

We provide microarray data comparing genome-wide differential expression and pathology throughout life in four lines of “amyloid” transgenic mice (mutant human APP, PSEN1, or APP/PSEN1) and “TAU” transgenic mice (mutant human MAPT gene). Microarray data were validated by qPCR and by comparison to human studies, including genome-wide association study (GWAS) hits. Immune gene expression correlated tightly with plaques whereas synaptic genes correlated negatively with neurofibrillary tangles. Network analysis of immune gene modules revealed six hub genes in hippocampus of amyloid mice, four in common with cortex. The hippocampal network in TAU mice was similar except that Trem2 had hub status only in amyloid mice. The cortical network of TAU mice was entirely different with more hub genes and few in common with the other networks, suggesting reasons for specificity of cortical dysfunction in FTDP17. This Resource opens up many areas for investigation. All data are available and searchable at http://www.mouseac.org. [Display omitted] •Gene expression in WT and five mouse dementia models; four ages; three brain regions•Validation of mouse models versus human genome data and network analysis•In Aβ mice, plaques show 1:1 correlation with immune gene expression; all ages•In old TAU mice, changes in immune and synaptic gene expression correlate with tangles In Alzheimer’s disease, should we target amyloid and plaques or TAU and tangles? Matarin et al. present a genome-wide gene expression and pathology resource comparing five transgenic mouse lines with only plaques or only tangles, allowing comparison of the separate effects of these pathologies throughout the life of the mouse.