Ex vivo modulation of tau phosphorylation by hyperpolarized light: implications for Alzheimer’s disease therapy

Alzheimer’s disease (AD) is characterized by amyloid-β accumulation and tau hyperphosphorylation, leading to neurodegeneration and cognitive decline. Photobiomodulation (PBM) has shown promise in mitigating AD pathology, yet its effects on tau remain poorly understood. We investigated the impact of high-polarized light (HPL; Bioptron Quantum Hyperlight, 350–3400 nm) on tau phosphorylation using an ex vivo rat brain slice model of synthetic torpor (ST), a reversible hypometabolic state inducing controlled tau hyperphosphorylation. Slices were incubated at physiological (37 °C) or hypometabolic (25 °C) temperatures and exposed to HPL for 10 or 20 minutes. Western blot analyses of Tau-1 (non-phosphorylated tau), p-GSK3β (Ser9), and p-T205 revealed that HPL increased Tau-1 levels in warm slices, indicating a shift toward reduced tau hyperphosphorylation. p-GSK3β modulation was variable, reflecting inter-animal differences and temperature-dependent kinase/phosphatase dynamics. Cold slices exhibited smaller, more heterogeneous responses, consistent with suppressed metabolic activity and attenuated PBM signaling. Site-specific p-T205 changes suggest transient kinase activation and redox signaling, compatible with an overall trend toward normalized tau phosphorylation. These results highlight how HPL can modulate tau phosphorylation ex vivo, with the most consistent effects under normothermic conditions. Despite limitations, our findings provide preliminary evidence supporting HPL/PBM as a potential therapeutic strategy for tauopathies. Future in vivo studies are warranted to elucidate mechanisms, optimize dosing, and explore glymphatic-mediated clearance in PBM-treated brains.