Neurological dysfunction associated with Down syndrome (DS) is the concomitant basal forebrain cholinergic neuron (BFCN) degeneration and onset of Alzheimer’s disease (AD) pathology. Previously, single population RNA sequencing analysis in the Ts65Dn (Ts) mouse model of DS revealed that the mitochondrial oxidative phosphorylation pathway was significantly impacted, where a large subset of genes within this pathway being downregulated. This study further examined oxidative phosphorylation pathway dysregulation in Ts mice by examining genes and encoded proteins within brain regions comprising the basocortical system at the start of BFCN degeneration. The dataset includes protein expression analysis and biochemical analysis of ATP levels data.