Arachidonic acid diet attenuates brain Aβ deposition in Tg2576 mice

Abstract The amyloid β-protein (Aβ) is believed to play a causative role in the development of Alzheimer׳s disease (AD). Because the amyloid precursor protein (APP), a substrate of Aβ, and β-secretase and γ-secretase complex proteins, which process APP to generate Aβ, are all membrane proteins, it is possible to assume that alterations in brain lipid metabolism modulate APP and/or Aβ metabolism. However, the role of polyunsaturated fatty acids in Aβ metabolism remains unknown. We report here that 9 months-treatment of Tg2576 mice with arachidonic acid (ARA)-containing (ARA+) diet prevented brain Aβ deposition in 17-month-old Tg2576 mice. APP processing to generate soluble APPα, CTF-β, and Aβ synthesis was attenuated in Tg2576 mice fed with the ARA+ diet. These findings suggest that ARA+ diet could prevent Aβ deposition through the alteration of APP processing in Tg2576 mice.