Thermal cycling-hyperthermia ameliorates Aβ25-35-induced cognitive impairment in C57BL/6 mice

•TC-HT rescues the cognitive performances in Y-maze and NOR tests better than HT.•TC-HT reduces Aβ and BACE1 levels better than conventional HT.•The expressions of insulin degrading enzyme are increased significantly via TC-HT.•The expression levels of antioxidative SOD2 protein are greatly enhanced via TC-HT.•TC-HT ameliorates neuroinflammation better than conventional HT. Despite continuation of some controversies, Alzheimer’s disease (AD), the most common cause of dementia nowadays, has been widely believed to derive mainly from excessive β-amyloid (Aβ) aggregation, that would increase reactive oxygen species (ROS) and induce neuroinflammation, leading to neuron loss and cognitive impairment. Existing drugs on Aβ have been ineffective or offer only temporary relief at best, due to blood–brain barrier or severe side effects. The study employed thermal cycling-hyperthermia (TC-HT) to ease the Aβ-induced cognitive impairments and compared its effect with continuous hyperthermia (HT) in vivo. It established an AD mice model via intracerebroventricular (i.c.v.) injection of Aβ25-35, proving that TC-HT is much more effective in alleviating its performance decline in Y-maze and novel object recognition (NOR) tests, in comparison with HT. In addition, TC-HT also exhibits a better performance in decreasing the hippocampal Aβ and β-secretase (BACE1) expressions as well as the neuroinflammation markers–ionized calcium-binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) levels. Furthermore, the study finds that TC-HT can elevate more protein expressions of insulin degrading enzyme (IDE) and antioxidative enzyme superoxide dismutase 2 (SOD2) than HT. In sum, the study proves the potential of TC-HT in AD treatment, which can be put into application with the use of focused ultrasound (FUS).