Color Dependence of OLED Phototherapy for Cognitive Function and Beta-Amyloid Reduction through ADAM17 and BACE1

Abstract

Previous studies have reported that 40 Hz visual stimulation (acute white light exposure) reduced A beta levels in Alzheimer's disease (AD) mouse model. However, whether different light colors distinctly regulate AD pathologies has not been well characterized. In the present study, an optimized organic light-emitting diode (OLED)-based visual stimulation platform was developed to provide uniform illumination without blind spots, and the color-dependent effects on cognitive function and amyloid-beta (A beta) pathology were investigated in 5xFAD mice, an A beta-overexpressing AD model. Acute exposure to white or red OLED light (1 h/day for 2 days) significantly improved cognitive function, reduced hippocampal A beta plaque accumulation via increasing ADAM17 activity, and downregulated proinflammatory cytokine IL-1 beta levels in 3-month-old 5xFAD mice, whereas green or blue OLED light did not produce these effects. In addition, chronic white and red OLED stimulation (1 h/day for 2 weeks) was shown to enhance recognition memory; however, only red light further diminished A beta plaque deposition by upregulating ADAM17 activity and suppressing BACE-1 activity without altering neuroinflammation in 6-month-old 5xFAD mice. Moreover, acute white and red OLED exposure (1 h, single session) was observed to enhance c-fos expression, which is associated with neural activation along the visual pathway, thereby suggesting a mechanistic link between light stimulation and cognitive enhancement. Taken together, these findings demonstrate that color-dependent visual stimulation may serve as a promising electroceutical strategy for AD, with red light uniquely combining memory enhancement, A beta reduction via ADAM17 upregulation and BACE1 suppression, and anti-inflammatory effects.