Long-term administration of Nano-PSO (GranaGard) to 5xFAD mice prevented age-dependent cognition and long-term memory deterioration

Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder, is characterized by progressive neuronal death, amyloid plaque deposits and oxidative damage leading to mitochondrial activity deficit. We have shown previously that Nano-PSO, a brain-targeted antioxidant composed of a nanodroplet formulation of Pomegranate Seed Oil (PSO), can delay disease onset and reduced disease burden significantly in animal models of genetic Creutzfeldt Jacob disease and multiple sclerosis. PSO comprises a unique component, Punicic acid (PA), also designated as Omega 5, a conjugated polyunsaturated fatty acid considered one of the strongest natural antioxidants. To establish whether this formulation could be beneficial also for AD, we administrated Nano-PSO to 5xFAD mice, a line established as a model for Alzheimer`s disease, constantly from infancy until 10 months old. Mice were tested for cognitive performance at two-time points (7 and 10 months old). Concomitantly, brain samples of wt and Tg mice both treated or untreated with Nano-PSO were analyzed for disease and expression of mitochondrial and oxidative response markers. We show here that age-related cognition deterioration in 5xFAD mice as compared to wt mice was significantly decreased by Nano-PSO treatment. This was also the case for treated 5XFAD mice performance in the T-maze and open field test, as well as in the novel object recognition test. Interestingly, also wt mice benefited with the Nano-PSO long-term treatment. Treated wt mice show a slight improvement compared to untreated mice in the different tasks. Immunostaining of mitochondrial markers indicates increased levels of cox4-1 in treated Tg brain, which was mostly absent in control Tg brain, indicating Nano-PSO administration prevented loss of mitochondrial normal function. In conclusion, our results show that Nano-PSO (GRANAGARD) administration can significantly prevent clinical and pathological symptoms of AD in model mice and therefore provide a rationale for a safe preventive treatment in humans at risk.