ECS-5 - High-fat and high cholesterol diet induces Alzheimer's like disease in mice.

Midlife hypercholesterolemia may contribute to onset of Alzheimer's disease (AD) in later life, however the mechanistic link between the two is poorly understood. Here we compared the effect of a 6-week high-fat/cholesterol diet (HFCD) in young (6-mo) mice with a genetic model of AD (3xTgAD), evaluating cognitive function, hippocampal synaptic plasticity, oxidative metabolism and the integrity of the blood-brain barrier (BBB). Despite producing a modest increase in serum cholesterol levels (10%), the HFCD induced significant alterations in cognitive function (novel object recognition, y-maze and water maze tests) comparable to those observed in age-matched 3xTgAD mice. At the synaptic level, HFCD and AD-genotype induced similar loss of LTP strength, accompanied by a decrease in maximal NMDAr-evoked NO production in hippocampal slices. HFCD-induced synaptic dysfunction was mainly post synaptic as revealed by PPF, while in the 3xTgAD mice a presynaptic component was also evident. HFCD also induced significant comprise of mitochondrial oxidative metabolism, including sparing capacity, while slightly affecting BBB integrity. We conclude that HFCD may, to an extent, induce Alzheimer's like disease in young mice similar to that observed in age-matched 3xTgAD mice. [ABSTRACT FROM AUTHOR]