ArticleiScience2026
High intensity 40 Hz flicker improves amyloid pathology and cognition with autophagy in 3xTg mice.
Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Gamma-frequency (40 Hz) flicker stimulation has emerged as a noninvasive approach for modulating Alzheimer's disease (AD)-related pathology, yet the influence of stimulation intensity remains unclear. We examined whether visual 40 Hz stimulation at different light intensities elicits distinct neurobiological effects in 19-24-week-old 3xTg-AD mice. High-intensity stimulation (1100-1500 lux) improved cognitive performance, modulated AMPK/mTOR signaling and autophagy-related markers, reduced neuronal Aβ burden, and preserved synaptic and neuronal integrity in both the primary visual cortex and hippocampus. In contrast, low-intensity stimulation (100-500 lux) primarily induced molecular changes in the primary visual cortex, with limited effects on hippocampal pathology or cognition. Pharmacological inhibition of autophagy with 3-methyladenine attenuated these effects. Together, these findings suggest graded responses to visual 40 Hz stimulation within the tested intensity range and implicate stimulation intensity as a contributing factor to region-specific and cognitive outcomes in early-stage AD models.
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