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

Authors

Dickson Wong, Robarts Research Institute
Dana N. Broberg, Robarts Research Institute
Jagroop Doad, Robarts Research Institute
Joseph U. Umoh, Robarts Research Institute
Miranda Bellyou, Robarts Research Institute
Chris J.D. Norley, Robarts Research Institute
David W. Holdsworth, Schulich School of Medicine & Dentistry
Manuel Montero-Odasso, The University of Western Ontario
Olivier Beauchet, University of Montreal
Cedric Annweiler, CHU Angers
Robert Bartha, Robarts Research InstituteFollow
Benedict Albensi

Document Type

Article

Publication Date

1-1-2021

Journal

Journal of Alzheimer's Disease

Volume

81

Issue

1

First Page

375

Last Page

388

URL with Digital Object Identifier

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-ß 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.