Neuroprotective Potential of Agaricus blazei Murrill: Modulating Amyloid-β Deposition and Oxidative Stress in Drosophila melanogaster (Supp. Figures).

Alzheimer's disease (AD) is a complex neurodegenerative disorder driven by Aβ proteotoxicity and chronic oxidative stress. The medicinal mushroom Agaricus blazei Murrill (AbM) is a promising source of neuroprotective compounds, particularly β-glucans, which may act via the gut-brain axis. We investigated the effects of AbM extract (0.01–0.2 mg/mL) in a Drosophila melanogaster model expressing human Aβ42. Following toxicological screening, the optimal non-toxic dose (0.01 mg/mL) was selected for subsequent analysis of redox biomarkers (GSH, H₂O₂, NO, protein carbonyls) and Aβ42 deposition. We employed SHapley Additive exPlanations (SHAP) analysis to interpret the therapeutic mechanism. The 0.01 mg/mL dose maintained systemic homeostasis, evidenced by stable levels of H₂O₂, GSH, NO, and protein carbonyls, confirming its non-toxic profile. Crucially, AbM supplementation significantly reduced the deposition of toxic Aβ42 in the eye and brain. SHAP analysis revealed that the neuroprotective effect is primarily driven by the modulation of acetylcholinesterase activity and Aβ42 levels, providing a 'white-box' view of the therapeutic outcome. AbM acts as a potent functional food, mitigating Aβ42 proteotoxicity and preserving redox balance in an in vivo model. These findings, supported by explainable AI, validate AbM as a promising, non-toxic intervention for AD management and warrant further investigation into its molecular mechanisms, particularly those related to β-glucan-mediated clearance pathways.