Here, we report that compared with Tg2576/ UCP1+/+ mice, Tg2576/UCP1−/− mice with elevated body temperatures demonstrated exacerbated AD-like pathologies due to increased Aβ, HSPs, phosphorylated and total tau, and tau kinases, as well as enhanced glial activation and decreased synaptic protein levels. This evidence concerns the gene UCP1 and Alzheimer disease.