Palmitic acid and docosahexaenoic acid opposingly regulate the expression of insulin-degrading enzyme in neurons.

Previous results show that treatment with saturated fatty acids, such as palmitic acid (PA), induces the pathology of Alzheimer's disease (AD), while treatment with polyunsaturated fatty acids, such as docosahexaenoic acid (DHA), protects against AD pathology. However, the pharmacological mechanism underlying these opposite effects of fatty acids on AD is not well understood. Here, we show that PA treatment significantly reduced the expression of insulin-degrading enzyme (IDE), an important protease responsible for the degradation of amyloid-beta (A beta) in neural cells, while incubation with DHA up-regulated IDE levels in primary hippocampal neurons. Moreover, pre-incubation with PA attenuated the DHA-induced IDE expression. Taken together, these results suggest the opposite effects of saturated fatty acids and polyunsaturated fatty acids on the expression of IDE, indicating a novel mechanism underlying the pharmacological function of fatty acids in AD intervention.