The presymptomatic treatment with <scp>3HFWC</scp> nanosubstance decreased plaque load in <scp>5XFAD</scp> mouse model of Alzheimer's disease

Introduction In the present study, we assessed the effects of the hyper-harmonized-hydroxylated fullerene–water complex (3HFWC) on Alzheimer&#39;s disease (AD) neuropathological hallmarks in 5XFAD mice, an AD animal model. Methods The 3-week-old 5XFAD mice were exposed to 3HFWC water solution ad libitum for 3 months in the presymptomatic phase of pathology. The functional effects of the treatment were confirmed through near-infrared spectroscopy (NIRS) analysis through machine learning (ML) using artificial neural networks (ANNs) to classify the control and 3HFWC-treated brain tissue samples. The effects of 3HFWC treatment on amyloid-β (Aβ) accumulation, plaque formation, gliosis, and synaptic plasticity in cortical and hippocampal tissue were assessed. Results The 3HFWC treatment significantly decreased the amyloid-β plaque load in specific parts of the cerebral cortex. At the same time, 3HFWC treatment did not induce the activation of glia (astrocytes and microglia) nor did it negatively affect synaptic protein markers (GAP-43, synaptophysin, and PSD-95). Conclusion The obtained results point to the potential of 3HFWC, when applied in the presymptomatic phase of AD, to interfere with amyloid plaque formation without inducing AD-related pathological processes such as neuroinflammation, gliosis, and synaptic vulnerability.