Abstract
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.
Highlights
During the development of Alzheimer’s disease (AD), changes in gene expression occur at many stages of disease progression
Mutations in amyloid precursor protein (APP) or presenilin 1 (PSEN1) or PSEN2 that lead to raised levels of a range of amyloidb (Ab) peptides are sufficient to result in Alzheimer’s disease in humans, phosphorylation of microtubule-associated protein tau and the development of tangles is an essential step in the course of the disease
Rate and Extent of Development of Amyloid Plaques and Neurofibrillary Tangles in Mice Used for Gene-Expression Studies As we aimed to identify and compare any expression changes that occur with the development of pathology in the different models, we investigated the level of amyloid plaque burden and phosphorylated tau pathology
Summary
During the development of Alzheimer’s disease (AD), changes in gene expression occur at many stages of disease progression. Amyloid and/or tau deposition and gliosis are thought to result in altered expression of genes including those of the immune system. These latter changes have often been thought of as secondary, and of little note, recent analyses have suggested that genetic variability in immune processes, with respect to microglial responses, is important in determining the risk of individuals presenting with the disease. The relative contribution of these two elements to different aspects of the disease is still a matter of controversy
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