High-fat diet aggravates amyloid-beta and tau pathologies in the 3xTg-AD mouse model

To investigate potential dietary risk factors of Alzheimer's disease (AD). triple transgenic (3xTg-AD) mice were exposed from 4 to 13 months of age to diets with a low n-3 n-6 polyunsaturated fatty acid (PUFA) ratio incorporated in either low-fat (5% w/w) or high-fat (35% w/w) formulas and compared with a control diet The n-3 n-6 PUFA ratio was decreased independently of the dietary treatments in the frontal cortex of 3xTg-AD mice compared to non-transgenic littermates. Consumption of a high-fat diet with a low n-3 n-6 PUFA ratio increased amyloid-beta (A beta) 40 and 42 concentrations in detergent-insoluble extracts of parieto-temporal cortex homogenates from 3xTg-AD mice Low n-3 n-6 PUPA intake ratio increased insoluble tau regardless of total fat consumption, whereas high-fat diet incorporating a low n-3 n-6 PUFA ratio also increased soluble tau compared to controls Moreover, the high-fat diet decreased cortical levels of the postsynaptic marker drebrin. while leaving presynaptic proteins synaptophysin. SNAP-25 and syntaxin 3 unchanged Overall, these results suggest that high-fat consumption combined with low n-3 PUPA intake promote AD-like neuropathology (C) 2008 Elsevier Inc All rights reserved