Transcranial 810 nm Pulsed Photobiomodulation Improves Learning and Reduces Aβ₄₂ Burden in APP/PS1 Mouse Model of Alzheimer’s Disease

Background: Alzheimer’s disease (AD) is a leading cause of dementia in older adults, and effective and widely applicable treatment options remain limited. Photobiomodulation (PBM) has shown promise for AD. However, reported estimates of the delivered dose after transcranial propagation vary widely, limiting translation from animal models to clinical settings. Objective: Building on our team’s prior clinical findings, this study evaluated whether an 810 nm/10 Hz pulsed PBM regimen improves cognitive performance and reduces Aβ₄₂ burden in APP/PS1 mice. Methods: APP/PS1 mice received PBM using an 810 nm LED pulsed at 10 Hz. Irradiation was delivered for 540 sec/day, 6 days/week, for 7 weeks, with a scalp-surface power density of 0.025 W/cm² and an energy density of 13.5 J/cm². Cognitive function was evaluated using the Morris water maze, and Aβ₄₂ burden was quantified by immunofluorescence. Results: Cortical and hippocampal Aβ₄₂ plaque burden was reduced, p < 0.01. Exploratory correlation analyses suggested an association between hippocampal Aβ₄₂ plaque number and reversal-learning performance in the histological subset, p = 0.02. The microglia-Aβ₄₂ colocalization ratio increased by 7.53%, p = 0.03, indicating enhanced spatial association between microglia and Aβ₄₂ after PBM. Conclusions: These findings support further evaluation of this 810 nm/10 Hz pulsed PBM regimen in AD mouse models and highlight the value of standardized PBM parameter reporting in preclinical studies.