For instance, the expression level of BDNF, defined as a hub gene in this study, is decreased in Alzheimer's disease by lowering the phosphorylated cyclic adenosine monophosphate (cAMP) response element binding (CREB) protein, which may lead to synaptic dysfunction and cognitive impairments [57]. This evidence concerns the gene BDNF and early-onset autosomal dominant Alzheimer disease.