Abstract
AbstractBackgroundVitamin D (vitD) deficiency and changes in body composition are frequently observed in Alzheimer’s disease (AD). The combination of memantine and vitD has been shown to protect cortical axons from glutamate toxicity and beta‐amyloid in AD. Further to these central effects, vitD and memantine may act peripherally to alter metabolism. The purpose of this study was to assess changes in body composition (lean, adipose, and skeletal tissue) in an AD mouse model due to vitD deprivation and subsequent treatment with memantine and memantine combined with high dose vitD supplementation.MethodMale APP/PS1 mice were randomized into four groups. Controls (n=14) received a standard diet throughout. The other three groups started a vitD deficient diet at month 6. At month 9, the VitD‐ group (n=14) remained on this diet, while the Mem&VitD‐ group (n=14) had memantine added, and the Mem&VitD+ group (n=14) had both memantine and 10 IU/g vitD added to their diet. Serum 25(OH)D3 levels were measured at months 6, 9, 12 and 15. Micro‐computed tomography scans were acquired at month 15 and segmented based on signal‐intensity to measure lean, adipose, and skeletal tissue mass and volume.ResultSerum 25(OH)D3 measurements confirmed that mice on vitD‐deficient diets had lower levels (89% decrease), and mice on the vitD‐enriched diet (Mem&VitD+) had higher levels (129% increase), of 25(OH)D3 relative to mice on the standard diet. No differences were observed in adipose or lean tissue mass and volume between the four groups, however, there was a significant increase in skeletal tissue mass (9.3% increase, p<0.05) and volume (9.2% increase, p<0.05), and bone mineral content (8.7% increase, p<0.01) in the Mem&VitD‐ group relative to controls.ConclusionWhile vitD deprivation did not affect body composition in APP/PS1 mice at 15 months, memantine increased absolute skeletal tissue in mice that were vitD‐deficient. However, memantine did not have this effect in mice that were vitD‐enriched. We conclude that combination treatment of memantine and vitD enrichment had no negative effects on body composition in the APP/PS1 mouse model. Future work should clarify whether vitD status impacts the effects of memantine on bone physiology in people with AD.
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