Effect of Memantine Treatment and Combination with Vitamin D Supplementation on Body Composition in the APP/PS1 Mouse Model of Alzheimer's Disease Following Chronic Vitamin D Deficiency

J Alzheimers Dis. 2021;81(1):375-388. doi: 10.3233/JAD-201137.

Abstract

Background: Vitamin D deficiency and altered body composition are common in Alzheimer's disease (AD). Memantine with vitamin D supplementation can protect cortical axons against amyloid-β exposure and glutamate toxicity.

Objective: To study the effects of vitamin D deprivation and subsequent treatment with memantine and vitamin D enrichment on whole-body composition using a mouse model of AD.

Methods: Male APPswe/PS1dE9 mice were divided into four groups at 2.5 months of age: the control group (n = 14) was fed a standard diet throughout; the remaining mice were started on a vitamin D-deficient diet at month 6. The vitamin D-deficient group (n = 14) remained on the vitamin D-deficient diet for the rest of the study. Of the remaining two groups, one had memantine (n = 14), while the other had both memantine and 10 IU/g vitamin D (n = 14), added to their diet at month 9. Serum 25(OH)D levels measured at months 6, 9, 12, and 15 confirmed vitamin D levels were lower in mice on vitamin D-deficient diets and higher in the vitamin D-supplemented mice. Micro-computed tomography was performed at month 15 to determine whole-body composition.

Results: In mice deprived of vitamin D, memantine increased bone mineral content (8.7% increase, p < 0.01) and absolute skeletal tissue mass (9.3% increase, p < 0.05) and volume (9.2% increase, p < 0.05) relative to controls. This was not observed when memantine treatment was combined with vitamin D enrichment.

Conclusion: Combination treatment of vitamin D and memantine had no negative effects on body composition. Future studies should clarify whether vitamin D status impacts the effects of memantine treatment on bone physiology in people with AD.

Keywords: 3-D imaging; Adipose tissue; Alzheimer’s disease; animal models; body composition; bone and bones; memantine; muscle; vitamin D; x-ray micro-CT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Body Composition / drug effects*
  • Dietary Supplements
  • Disease Models, Animal
  • Dopamine Agents / pharmacology
  • Dopamine Agents / therapeutic use*
  • Male
  • Memantine / pharmacology
  • Memantine / therapeutic use*
  • Mice
  • Mice, Transgenic
  • Presenilin-1 / genetics
  • Vitamin D / pharmacology
  • Vitamin D / therapeutic use*
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / drug therapy*
  • Vitamin D Deficiency / genetics

Substances

  • Amyloid beta-Protein Precursor
  • Dopamine Agents
  • Presenilin-1
  • Vitamin D
  • Memantine