Sauna-like conditions or menthol treatment reduce tau phosphorylation through mild hyperthermia

In Alzheimer's disease (AD), hyper-phosphorylation and aggregation of tau correlate with clinical pro-gression and represent a valid therapeutic target. A recent 20-year prospective study revealed an associ-ation between moderate to high frequency of Finnish sauna bathing and a lower incidence of dementia and AD, but the molecular mechanisms underlying these benefits remain uncertain. Here, we tested the hypothesis that sauna-like conditions could lower tau phosphorylation by increasing body temperature. We observed a decrease in tau phosphorylation in wild-type and hTau mice as well as in neuron-like cells when exposed to higher temperatures. These effects were correlated with specific changes in phos-phatase and kinase activities, but not with inflammatory or heat shock responses. We also used a drug strategy to promote thermogenesis: topical application of menthol, which led to a sustained increase in body temperature in hTau mice, concomitant with a significant decrease in tau phosphorylation. Our re-sults suggest that sauna-like conditions or menthol treatment could lower tau pathology through mild hyperthermia, and may provide promising therapeutic strategies for AD and other tauopathies. (c) 2022 Elsevier Inc. All rights reserved.

Automated summary

The study found that sauna bathing or menthol treatment may lower tau protein phosphorylation levels by increasing body temperature, potentially serving as effective therapeutic strategies for Alzheimer's disease and other tauopathies.