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Literature Review | Effects of Memantine and Vitamin D Treatment on Body Composition in APP/PSI Mice

Journal of Alzheimer’s Disease IF:4.5

Introduction

In Alzheimer’s disease (AD) research, vitamin D deficiency and alterations in body composition are relatively common. Supplementation with vitamin D and treatment with memantine—a medication used to treat AD—can protect cortical axons from amyloid‑β–induced damage and toxicity. In this study, we employed an APP/PS1 mouse model of vitamin D deficiency to investigate… The effect of memantine combined with vitamin D treatment on body composition changes in APP/PS1 mice 。

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I. Experimental Methods:

Mouse model: APP/PS1 mice (hereinafter referred to as APP)

①Control group: fed a normal diet (n = 14);

②VitD group: Starting at 6 months of age, fed a diet deficient in vitamin D (n = 14);

③Mem&VitD group: Starting at 6 months of age, animals were fed a diet deficient in vitamin D; from 9 months of age, they received memantine treatment (n = 14).

④Mem&VitD+ group: Starting at 6 months of age, animals were fed a diet deficient in vitamin D; beginning at 9 months, they received memantine treatment and vitamin D supplementation (n = 14).

Serum samples were collected at 6, 9, 12, and 15 months of age to measure vitamin D levels; at 15 months, micro-CT imaging was performed to analyze the mice’s body composition. 。

Figure 1

II. Results:

1. Serum vitamin D assay results (Figure 2) ):

① In the control group, serum vitamin D levels did not show any significant changes across the time points (though body weight did change).

②In the VitD group, serum vitamin D levels decreased significantly, with an average reduction of 83%.

③The Mem&VitD group also showed a sustained and significant decrease in serum levels;

④In the Mem&VitD+ group, vitamin D levels declined significantly by month 9; by months 12 and 15, vitamin D concentrations were not only higher than at month 9 but also more than twice as high as at month 6.

Figure 2: Serum Vitamin D Test Results

In summary, serum vitamin D levels in mice can be modulated through dietary intake. Compared with mice fed a vitamin D–deficient diet, those consuming a vitamin D–rich diet exhibited serum levels more than tenfold higher.

2. Micro-CT findings at 15 months of age (Figure 3):

(Figure 3) Micro-CT legend: adipose tissue (yellow), lean tissue (red), or bone tissue (white).

① There were no differences in total mass or volume among mice across the different treatment groups, and the total mass measured by the gravimetric method did not differ significantly from that obtained by micro-CT, thereby validating the feasibility of using micro-CT for quantifying tissue mass. (Figure 4)

Figure 4

②Micro-CT analysis was performed to assess the weight and volume of lean tissue, adipose tissue, and bone tissue. The results showed that the Mem&VitD group exhibited significantly greater bone tissue weight and volume compared with the control group; this was the only statistically significant difference observed between the two groups. (Figure 5)

Figure 5

③ Using CT-derived bone volume, we calculated the mouse bone mineral content (BMC) and bone mineral density (BMD). The Mem&VitD group exhibited a significantly higher BMC compared with the control group, whereas no significant difference was observed in BMD. (Figures 6–7)

Figure 6

Figure 7

Insufficient dietary intake leads to a decline in serum vitamin D levels, whereas an adequate diet results in elevated serum vitamin D levels; in the control group, serum vitamin D levels remained unchanged throughout the study.

In vitamin D–deficient mice, after 15 months of memantine treatment, bone tissue volume and mass, as well as bone mineral content, increased; however, combined memantine and vitamin D treatment had no effect on the overall composition of lean tissue, adipose tissue, or bone tissue.

III. Discussion

Vitamin D deficiency did not affect body weight, body composition, or bone mineral density in 15-month-old mice, contrary to the conventional belief that a 1.15% decrease in vitamin D levels is associated with a one-unit increase in BMI.

In the vitamin D–deficient group, mouse BMD did not show any significant change, possibly because a dietary calcium level of 0.5%—and even 0.4% or 0.1%—can maintain calcium homeostasis. This suggests that the diet may contain sufficient calcium to compensate for the reduced calcium absorption caused by vitamin D deficiency, thereby preserving skeletal physiology in vitamin D–deficient mice.

Mem&VitD—In mice, bone tissue and bone mineral content were increased; the underlying mechanism may be that memantine, as an NMDAR antagonist, modulates osteoclast and osteoblast activity. Meanwhile, supplementation with Mem&VitD plus vitamin D can further stimulate enhanced bone resorption.

Memantine had no significant effect on the body volume or body weight of AD mice; however, some studies have reported that the drug exerts pronounced effects on obesity, insulin resistance in type 2 diabetes, and weight gain, among other outcomes, with the underlying mechanisms remaining to be elucidated.

When memantine is used as monotherapy, bone tissue mass and volume are significantly increased in the absence of vitamin D. Combined treatment with memantine and a vitamin D‑rich diet maintains bone tissue mass and volume at levels comparable to those observed in mice fed either a normal diet or a vitamin D–deficient diet.

In this study, high-dose dietary supplementation with vitamin D increased serum vitamin D levels in APP mice by 2.3-fold compared to those on a standard diet, potentially exerting neuroprotective effects via antioxidant mechanisms, neuronal calcium homeostasis, and immune modulation. In clinical trials, we evaluated a high-dose formulation, and the results indicated that the high dose can enhance cognitive function in humans.

IV. Conclusion

Vitamin D deficiency in mice does not alter body composition in lean tissue, adipose tissue, or bone; combined treatment with memantine and vitamin D supplementation enhances vitamin D absorption in an Alzheimer’s disease mouse model without adversely affecting body composition.

Literature Reference News: https://doi.org/10.3233/JAD-201137

Aniphe BioLab can provide you with:

1. Mouse models including APP/PSI, APP/PSI/Tau, 5XFDA, and littermate controls for APP;

2. Body Composition Analysis Service:

① Micro-CT: for fat, lean meat, and bone;

② Awake Small Animal Body Composition Analyzer: It can measure the fat and lean tissue content of small animals while they are awake, and provides distribution imaging (as shown below):