Arachidonic or docosahexaenoic acid diet prevents memory impairment in Tg2576 mice

It is believed that the amyloid β-protein (Aβ) plays a causative role in the development of Alzheimer's disease (AD). The amyloid-β protein precursor (AβPP), a substrate of Aβ, and β-secretase and β-secretase complex proteins, which process AβPP to generate Aβ, are all membrane proteins. Thus, it is reasonable to assume that alterations in brain lipid metabolism modulate AβPP and/or Aβ metabolism. However, the role of cellular polyunsaturated fatty acids in AβPP processing has not been completely understood yet.We report here that 4 months of treatment of Tg2576 mice with an arachidonic acid (ARA)-or a docosahexaenoic acid (DHA)-containing (ARA+ or DHA+) diet prevented memory impairment at 13 months of age. Although, AβPP processing to generate soluble AβPP and induce Aβ synthesis was enhanced, Aβ1-42/Aβ1-40 ratio decreased in 14-monthold Tg2576 mice fed with the ARA+ or DHA+ diet. The ARA+ or DHA+ diet did not alter the AβPP levels and the expression levels of Aβ-degrading enzymes. In cortical primary neuron cultures, ARA or DHA treatment also increased soluble AβPP and Aβ1-40 levels, and decreased Aβ 1-42/Aβ 1-40 ratio, which are similar to what were observed in Tg2576 mice fed with ARA+ or DHA+ diet. These findings suggest that not only the DHA+ diet, but also the ARA+ diet could prevent cognitive dysfunction in Tg2576 mice through the alteration of AβPP processing.