Deuterated polyunsaturated fatty acids reduce brain lipid peroxidation and hippocampal amyloid β-peptide levels, without discernable behavioral effects in an APP/PS1 mutant transgenic mouse model of Alzheimer's disease.

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 (amyloid precursor protein/presenilin 1 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 hydrogenated-PUFA control diet, those fed D-PUFA for 5 months exhibited high levels of incorporation of deuterium into arachidonic acid and docosahexaenoic acid, and reduced concentrations of lipid peroxidation products (F2 isoprostanes and neuroprostanes), in the 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 hydrogenated-PUFA. We conclude that a D-PUFA diet reduces the brain tissue concentrations of both arachidonic acid and docosahexaenoic acid oxidation products, as well as the concentration of Aβs.

• Authors: Sophia M Raefsky, Ran Furman, Ginger Milne, Erik Pollock, Paul Axelsen, Mark P Mattson, Mikhail S Shchepinov
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 66 Pg. 165-176 (06 2018) ISSN: 1558-1497 [Electronic] United States
• PMID: 29579687 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Published by Elsevier Inc.

Chemical References

• Amyloid beta-Peptides
• Fatty Acids, Unsaturated
• Deuterium

Topics

• Alzheimer Disease (metabolism, psychology)
• Amyloid beta-Peptides (metabolism)
• Animals
• Depression, Chemical
• Deuterium
• Dietary Supplements
• Disease Models, Animal
• Fatty Acids, Unsaturated (administration & dosage, chemistry, pharmacology)
• Female
• Hippocampus (metabolism)
• Lipid Peroxidation (drug effects)
• Male
• Memory
• Mice, Transgenic
• Spatial Learning