E2F Transcription Factor 8 Contributes to the Pathogenesis of Alzheimer's Disease Accompanied with Decreased Expression of Matrix Metalloproteinase-9 and B-cell Lymphoma 2.

Export Evidence suggests that changes in gene expression play an important role in the development and progression of Alzheimer’s disease (AD). Although many genes have already been identified, there are other genes potentially involved in this process but have not been identified. To further investigate the differences in gene expression profiles between amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice and wild-type (WT) mice, we have employed RNA sequencing to analyze the transcriptome and identified candidate genes involved in the pathogenesis of AD. Because melatonin was shown to alleviate the pathology of AD and rescue the cognitive impairment in animal models of AD, we have also included APP/PS1 mice that received melatonin treatment for comparison of gene expression profiles. Our results reveal that the E2F transcription factor 8 (E2f8) gene is differentially expressed between APP/PS1 mice and WT mice, and E2F8 contributes to the pathogenesis of AD. This is probably due to E2F8-mediated suppression of the expression of matrix metalloproteinase-9 and B-cell lymphoma 2 that results in amyloid-beta accumulation and neuronal apoptosis.