This article investigates the potential therapeutic effects of mild hyperthermia, induced through sauna-like conditions or menthol treatment, on tau phosphorylation, a key pathological feature in Alzheimer's disease (AD) and other tauopathies. The abnormal hyperphosphorylation of tau protein promotes the formation of neurofibrillary tangles, which correlate with the neurodegeneration and clinical progression of AD. Although tau phosphorylation has long been considered a valid target for therapeutic intervention, no successful treatments have been developed thus far. Previous studies indicated that hypothermia induces tau hyperphosphorylation, leading the researchers to hypothesize that mild hyperthermia could have the opposite effect, reducing tau phosphorylation.

Building on a 20-year Finnish study that found regular sauna bathing to be associated with a reduced risk of dementia and AD, the researchers set out to explore the underlying molecular mechanisms. In this study, they exposed wild-type and hTau mice to elevated temperatures akin to sauna conditions, which led to a significant reduction in tau phosphorylation. These findings were further supported by cellular experiments using neuron-like cells, where similar temperature elevations resulted in decreased tau phosphorylation. The researchers found that these effects were linked to changes in phosphatase and kinase activities, without any significant impact on inflammation or heat shock protein responses, which are often associated with heat-induced stress.

Additionally, the study introduced a novel approach using menthol treatment to induce thermogenesis. In hTau mice, topical menthol application led to a sustained increase in body temperature and a concurrent reduction in tau phosphorylation. These results suggest that sauna-like hyperthermia or thermogenic treatments such as menthol could potentially serve as therapeutic strategies for AD and other tauopathies. By offering a new pathway for mitigating tau-related pathology, the research highlights the possibility of non-invasive, accessible treatments aimed at reducing the progression of tau-related neurodegenerative diseases.