D-PUFAs reduce brain lipid peroxidation and hippocampal amyloid beta-peptide levels
Abstract
Alzheimer’s disease (AD) involves progressive deposition of amyloid β-peptide (Aβ), synapse loss and neuronal death, which occur in brain regions critical for learning and memory. Considerable evidence suggests that lipid peroxidation contributes to synaptic dysfunction and neuronal degeneration, both upstream and downstream of Aβ pathology. Recent findings suggest that lipid peroxidation can be inhibited by replacement of polyunsaturated fatty acids (PUFA) with isotope-reinforced (deuterated) PUFA (D-PUFA), and that D-PUFA can protect neurons in experimental models of Parkinson’s disease. Here we determined whether dietary D-PUFA would ameliorate Aβ pathology and/or cognitive deficits in a mouse model of AD (APP/PS1 double mutant transgenic mice). The D-PUFA diet did not ameliorate spatial learning and memory deficits in the AD mice. Compared to mice fed an H-PUFA control diet, those fed D-PUFA for 5 months exhibited high levels of incorporation of deuterium into arachidonic acid and docosahexanoic acid, and reduced concentrations of lipid peroxidation products (F2 isoprostanes and neuroprostanes), in brain tissues. Concentrations of Aβ40 and Aβ38 in the hippocampus were significantly lower, with a trend to reduced concentrations of Aβ42, in mice fed D-PUFA compared to those fed H-PUFA. We conclude that a D-PUFA diet reduces the brain tissue concentrations of both ARA and DHA oxidation products, as well as the concentration of Aβs.
