Effects of chain length of saturated fatty acids on Aβ generation in SH-SY5Y cells

Many studies have shown that saturated fat diet increases the risk of AD. Recently saturated very long chain fatty acids (VLCFAs) have been found be accumulated in AD patients. The variety of saturated fatty acids are found in the diets and human bodies. However, it is not clear which one or more fatty acids are involved in AD pathogenesis. This study investigated the effects of three saturated fatty acids with different carbon chain length (C16:0, C20:0, and C26:0) on amyloid precursor protein (APP) processing and amyloid-β peptide (Aβ) generation. Here, SH-SY5Y cells were treated with vehicle, C16:0, C20:0, and C26:0 (10 μmol/L, 24 h). Compared to the vehicle, C16:0 did not cause any significantly change in APP processing and Aβ generation. C20:0 and C26:0 increased Aβ levels and the expressions of APP, β- and γ-secretase and decreased the expression of α-secretase, and C26:0 had the strongest effects among three fatty acids. Moreover, C20:0 and C26:0 significantly increased reactive oxygen species (ROS), and C16:0 had no such effect. These data indicate that saturated fatty acids with different carbon chain length (C16:0, C20:0 and C26:0) have different effects on the process of Aβ generation, and fatty acids with longer chain (C20:0 and C26:0) have more potential to promote Aβ production and an underlying mechanism of fatty acids action may be related to the elevated oxidative stress. This work supports saturated very long chain fatty acids may play a potential role in the pathogenesis of AD.