Sever eIn Vivo Hyper-Homocysteinemi ais no tAssociate dwit hElevatio no fAmyloid-β Peptides in the Tg2576 Mice

Since hyper-homocysteinemia (HHcy) was recognized as a risk factor for Alzheimer's disease (AD), many studies tried to induce HHcy in animal models to investigate its effect on amyloid-β protein precursor (AβPP) metabolism. Previous reports found that HHcy induced in AD transgenic mouse models, by either feeding a methionine-enriched diet or vitamin Bs deficient diet, is associated with elevation of amyloid-β (Aβ) levels. However, there is no data available on the effect of dietary intervention which combines both excessive methionine and low levels of vitamin Bs on amyloidogenesis in any of these models. In the current study, we investigated the effect of a combination diet, which was both enriched in methionine and deficient in folate, vitamin B6 and B12, in an AD mouse model, the Tg2576. We found that 7 months treatment of this diet induced severe HHcy in these mice with plasma homocysteine level higher than 150 µM. However, no difference was detected in brain Aβ levels or deposition between the diet-treated and control group. As shown by western blot, severe HHcy did not alter the steady state levels of proteins involved in AβPP metabolism, either. These results demonstrate that this combination diet-induced severe HHcy does not influence amyloidogenesis in vivo.