Docosahexaenoic acid-induced amelioration on impairment of memory learning in amyloid β-infused rats relates to the decreases of amyloid β and cholesterol levels in detergent-insoluble membrane fractions

We investigated the effects of dietary administration of docosahexaenoic acid (DHA; C22:6n-3) on the levels of amyloid β (Aβ) peptide (1-40) and cholesterol in the nonionic detergent Triton 100×-insoluble membrane fractions (DIFs) of the cerebral cortex and, also, on learning-related memory in an animal model of Alzheimer's disease (AD) rats infused with Aβ peptide (1-40) into the cerebral ventricle. The infusion increased the levels of Aβ peptide and cholesterol in the DIFs concurrently with a significant increase in reference memory errors (measured by eight-arm radial-maze tasks) compared with those of vehicle rats. Conversely, the dietary administration of DHA to AD-model rats decreased the levels of Aβ peptide and cholesterol in the DIFs, with the decrease being more prominent in the DHA-administered rats. Regression analysis revealed a significant positive correlation between Aβ peptide and each of cholesterol, palmitic acid and stearic acid, and between the number of reference memory errors and each of cholesterol, palmitic, stearic and oleic acid; moreover, a significant negative correlation was observed between the number of reference memory errors and the molar ratio of DHA to palmitic plus stearic acid. These results suggest that DHA-induced protection of memory deficits in AD-model rats is related to the interactions of cholesterol, palmitic acid or stearic acid with Aβ peptides in DIFs where DHA ameliorates these interactions.