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Alzheimer disease (AD) is a devastating neurological disorder, which initiates from hippocampus and proliferates to cortical regions. The neurons of hippocampus require higher energy to preserve the firing pattern. In AD, aberrant energy metabolism is the critical factor for neurodegeneration. However, the reason for the energy crisis in hippocampus neurons is still unresolved. Transcriptome analysis enables us in understanding the underlying mechanism of energy crisis. In this study, we identified variants/differential gene/transcript expression profiles from hippocampus RNA-seq data. We predicted the effect of variants in transcription factor (TF) binding using in silico tools. Further, a hippocampus-specific co-expression and functional interaction network were designed to decipher the relationships between TF and differentially expressed genes (DG). Identified variants predominantly influence TF binding, which subsequently regulates the DG. From the results, we hypothesize that the loss of vascular integrity is the fundamental attribute for the energy crisis, which leads to neurodegeneration.