Effects of memantine and high dose vitamin D on gait in the APP/PS1 mouse model of Alzheimer’s disease following vitamin D deprivation

Abstract

ABSTRACTBackgroundAltered gait is a frequent feature of Alzheimer’s disease (AD), as is vitamin D deficiency. Treatment with memantine and vitamin D can protect cortical axons from exposure to amyloid-β and glutamate toxicity, suggesting this combination may mitigate altered gait in AD.ObjectiveInvestigate the effects of vitamin D deprivation and subsequent treatment with memantine and vitamin D enrichment on gait performance in APPswe/PS1dE9 mice.MethodsMale APPswe/PS1dE9 mice were split into four groups (n=14 each) at 2.5 months of age. A control group was fed a standard diet throughout while the other three groups started a vitamin D-deficient diet at month 6. The VitD− group remained on this deficient diet for the rest of the study. At month 9, the remaining two groups began treatment with either memantine alone or memantine combined with 10 IU/g of vitamin D. Gait performance was assessed at months 6, 9, 12, and 15.ResultsVitamin D deprivation led to a 13% increase in hind stride width by month 15 (p<0.001). Examination of the treatment groups at month 15 revealed that mice treated with memantine alone still showed an increase in hind stride width compared to controls (p<0.01), while mice treated with memantine and vitamin D did not (p=0.21).ConclusionVitamin D deprivation led to impaired postural control in the APPswe/PS1dE9 model. Treatment with memantine and vitamin D, but not memantine alone, prevented this impairment. Future work should explore the potential for treatments incorporating vitamin D supplementation to improve gait in people with AD.