Impaired spatial memory in APP-overexpressing mice on a homocysteinemia-inducing diet.


Consumption of a diet that significantly elevates homocysteine (homocysteinemia) induces cell death in the CA3 hippocampal subfield in amyloid precursor protein (APP) over-expressing transgenic mice but not in wild-type controls. We assessed behavioral and other neuropathological effects of a homocysteinemia-inducing diet in aged APP-overexpressing mice. Starting at 16-18 months of age, mice were fed either a treatment diet lacking folate, choline, and methionine, and supplemented with homocysteine, or a control diet containing normal amounts of folate, choline and methionine but no homocysteine. After 5 months on the experimental diets, performance on a delayed non-matching-to-position working-memory task was unimpaired. In contrast, spatial reference memory in the water maze was impaired in transgenic mice on the treatment diet. Transgenic mice had higher homocysteine levels than wild-type mice even when fed the control diet, suggesting an effect of genotype on homocysteine metabolism. Methyl-donor deficiency did not alter amyloid deposition in the transgenic mice. These results suggest that disrupted homocysteine metabolism may induce Abeta-associated memory impairments and neurodegeneration in APP overexpressing mice.


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@article{Bernardo2007ImpairedSM, title={Impaired spatial memory in APP-overexpressing mice on a homocysteinemia-inducing diet.}, author={Alexandra Bernardo and Meghan McCord and Aron M Troen and John D. Allison and Michael P. McDonald}, journal={Neurobiology of aging}, year={2007}, volume={28 8}, pages={1195-205} }