Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by microtubule destabilization, neuroinflammation, and tau pathology. Among the proposed therapeutic approaches, acetyl-11-keto-β-boswellic acid (AKBA), a bioactive triterpene from Boswellia serrata, has gained attention due to its multiple neuroprotective mechanisms, including microtubule stabilization, anti-inflammatory activity, antioxidant effects, and promotion of neurogenesis. In this study, we aimed to investigate the neuroprotective effect of AKBA against tau oligomer-induced cytotoxicity in SH-SY5Y neuroblastoma cells. Recombinant human tau protein was expressed, purified, and oligomerized, and the formation of oligomers was confirmed by thioflavin T fluorescence and dynamic light scattering (DLS). SH-SY5Y cells were then treated with AKBA and exposed to tau oligomers. Cell viability was assessed via MTT assay, and apoptosis was evaluated by flow cytometry. The morphology of tau aggregates was visualized using transmission electron microscopy. Our findings demonstrated that AKBA significantly reduced tau oligomer-induced cytotoxicity and enhanced cell viability. These results suggest that AKBA, through its multifaceted protective mechanisms, holds promise as a potential therapeutic agent for the treatment of tauopathies such as Alzheimer's disease. Not applicable.

BackgroundCognitive fatigue is a frequently reported and debilitating symptom of long COVID, yet effective therapeutic interventions remain limited. Anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) has been proposed as a promising approach to modulate fatigue-related neural networks. To comprehensively assess cognitive fatigue, the integration of subjective and objective behavioral and electrophysiological measures of induced state fatigue is essential.MethodsThis double-blind, randomized, sham-controlled study investigated the effects of four consecutive daily sessions of 30-minute anodal tDCS over the left dlPFC on subjective and objective markers of cognitive state fatigue in individuals with long COVID. The present paper focuses on secondary outcomes, including subjective state fatigue ratings via visual analogue scales, behavioral performance indices, and electrophysiological markers such as temporal alterations of frontal theta and occipital alpha activity as well as p50 sensory gating.ResultsForty participants received either verum or sham tDCS while completing a gamified adaptive Go/No-Go task. Before and after the stimulation period, cognitive state fatigue was reliably induced using the AX-Continuous Performance Task (AX-CPT). Although tDCS did not significantly affect subjective state-fatigue ratings or behavioral performance, our findings indicate that verum stimulation may stabilize fatigue-related changes in occipital alpha power. No immediate stimulation-related improvements were found in the Go/No-Go task.ConclusionsThese findings indicate that while tDCS may modulate neurophysiological correlates of cognitive state fatigue, its impact on subjective experience and behavioral performance remain limited under the current protocol. These results, however, underscore the importance of including neurophysiological endpoints in intervention research and highlight the need for developing more robust and individualized stimulation protocols. Future studies should consider extended stimulation regimens, alternative task paradigms, and more sensitive behavioral measures to further elucidate the neuromodulatory potential of tDCS in long COVID-related cognitive fatigue.Trial registrationdrks.de Identifier: DRKS00031294, date of registration: 17.02.2023