Abdel_2023_Pharmaceutics_15_

Alzheimer's disease (AD) is a neurodegenerative disorder that jeopardizes the lives of diagnosed patients at late stages. This study aimed to assess, for the first time, the efficiency of germanium dioxide nanoparticles (GeO(2)NPs) in mitigating AD at the in vivo level compared to cerium dioxide nanoparticles (CeO(2)NPs). Nanoparticles were synthesized using the co-precipitation method. Their antioxidant activity was tested. For the bio-assessment, rats were randomly assigned into four groups: AD + GeO(2)NPs, AD + CeO(2)NPs, AD, and control. Serum and brain tau protein, phosphorylated tau, neurogranin, amyloid beta peptide 1-42, acetylcholinesterase, and monoamine oxidase levels were measured. Brain histopathological evaluation was conducted. Furthermore, nine AD-related microRNAs were quantified. Nanoparticles were spherical with diameters ranging from 12-27 nm. GeO(2)NPs exhibited a stronger antioxidant activity than CeO(2)NPs. Serum and tissue analyses revealed the regression of AD biomarkers to almost control values upon treatment using GeO(2)NPs. Histopathological observations strongly supported the biochemical outcomes. Then, miR-29a-3p was down-regulated in the GeO(2)NPs-treated group. This pre-clinical study substantiated the scientific evidence favoring the pharmacological application of GeO(2)NPs and CeO(2)NPs in AD treatment. Our study is the first report on the efficiency of GeO(2)NPs in managing AD. Further studies are needed to fully understand their mechanism of action.