Deuterium‐reinforced polyunsaturated fatty acids improve cognition in a mouse model of sporadic Alzheimer's disease

Oxidative damage resulting from increased lipid peroxidation (LPO) is considered an important factor in the development of late onset/age‐related Alzheimer's disease (AD). Deuterium‐reinforced polyunsaturated fatty acids (D‐PUFAs) are more resistant to the reactive oxygen species‐initiated chain reaction of LPO than regular hydrogenated (H‐) PUFAs. We investigated the effect of D‐PUFA treatment on LPO and cognitive performance in aldehyde dehydrogenase 2 (Aldh2) null mice, an established model of oxidative stress‐related cognitive impairment that exhibits AD‐like pathologies. Mice were fed a Western‐type diet containing either D‐ or H‐PUFAs for 18 weeks. D‐PUFA treatment markedly decreased cortex and hippocampus F2‐isoprostanes by approximately 55% and prostaglandin F2α by 20–25% as compared to H‐PUFA treatment. D‐PUFAs consistently improved performance in cognitive/memory tests, essentially resetting performance of the D‐PUFA‐fed Aldh2−/− mice to that of wild‐type mice fed a typical laboratory diet. D‐PUFAs therefore represent a promising new strategy to broadly reduce rates of LPO, and combat cognitive decline in AD.