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 beta (A beta) peptide (1-40) and cholesterol in the nonionic detergent Triton 100x-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 A beta peptide (1-40) into the cerebral ventricle. The infusion increased the levels of A beta 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 A beta peptide and cholesterol in the DlFs, with the decrease being more prominent in the DHA-administered rats. Regression analysis revealed a significant positive correlation between A beta 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 A beta peptides in DIFs where DHA ameliorates these interactions. (c) 2005 Elsevier B.V. All rights reserved.