Researchers at Université Laval in Canada demonstrated that aging mice in a model of Alzheimer’s disease (AD) were less able to regulate their body temperatures, and when exposed to a cold environment showed increased AD manifestations. These results suggest correction of thermoregulation might be a therapeutic avenue for Alzheimer’s.
The accentuated incidence of AD in older people is accompanied by a reduction in energy metabolism and core body temperature. Researchers investigated if changes in body temperature regulation would amplify the debilitating manifestations of the disease, and if such effects would manifest in a vicious circle, as areas of the brain involved in thermoregulation are affected in Alzheimer’s.
To test the hypothesis, the team used a mouse model of AD, the 3xTg-AD, that presents the hallmarks of the disease, including beta-amyloid production, formation of plaque, synapse loss, and memory loss starting at 6 months. Compared to normal mice, the AD mice were less effective in maintaining their body temperature, spontaneously developing a lower basal temperature as they grew older. The difference between transgenic and normal control mice reached almost 1° Celsius (about 1.8° Fahrenheit) at 12 months of age. Moreover, AD mice were more vulnerable to low temperatures, and clinical manifestations of AD more noticeable when they were exposed to a colder environment. After a 24-hour exposure to cold (4°C/39°F), key pathological markers of AD were worse, namely abnormal tau protein and loss of synaptic proteins. Raising the body temperature in the transgenic animals improved memory, and mitigated amyloid and synapse pathologies within a week.
Researchers believe that such findings hint at a possible new therapeutic avenue, warranting investigation in people. “Our findings suggest that it is worth exploring the treatment of thermoregulation among seniors suffering from Alzheimer’s,” Professor Frédéric Calon, the study’s lead author, said in a news release. “If our conclusions are confirmed, it would be a relatively easy therapeutic option to implement because body temperature can be increased through physical activity, diet, drugs, or simply by increasing the ambient temperature.”