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

Alexandra Bernardo, Meghan McCord, Aron M. Troen, John D. Allison, Michael P. McDonald*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


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 Aβ-associated memory impairments and neurodegeneration in APP overexpressing mice.

Original languageAmerican English
Pages (from-to)1195-1205
Number of pages11
JournalNeurobiology of Aging
Issue number8
StatePublished - Aug 2007
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the National Institute of Aging (AG022439), the National Institute of Child Health and Development (HD015052), and the U.S. Department of Agriculture under cooperative agreement No. 58-1950-9-001. Some of the behavioral experiments were conducted within the Murine Neurobehavioral Laboratory core facility ( ).


  • Alzheimer
  • Amyloid
  • Behavior
  • Delayed conditional discrimination
  • Delayed non-matching to position
  • Folate
  • Folic acid
  • Homocysteine
  • Learning
  • Memory
  • Transgenic
  • Water maze


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