Myostatin Is Associated With Cognitive Decline in an Animal Model of Alzheimer’s Disease

  • Yung-Shuen Lin
  • Fang-Yu Lin
  • Ya-Hsin Hsiao


With aging, there are progressive functional declines in multiple organ systems. One of the major physiological problems observed in aged people is skeletal muscle loss. This age-related muscle loss causes muscle weakness and disability, which in turn might reduce the quality of life in older adults and lead to the progression of several diseases, particularly Alzheimer’s disease (AD). Some researchers have hypothesized that loss of muscle mass and strength is linked to the risk of developing AD. In addition, unintended weight loss often occurs in AD patients and might reflect dementia severity. However, the causal relationship between muscle atrophy and cognitive deficits in AD is unclear. We found that double transgenic amyloid precursor protein and presenilin 1 (APP/PS1) mice that co-express APP and PS1 at older ages exhibited lower body weight and lean tissue mass than sex- and age-matched wild-type (WT) mice. In addition, muscle atrophy and the extent of memory decline were strongly correlated in APP/PS1 mice. Myostatin levels in the gastrocnemius (GAS) muscle of 12-month-old APP/PS1 mice were elevated. We determined that the cellular and molecular mechanism of muscle atrophy was through the ubiquitin-proteasome pathway. Furthermore, myostatin knockdown in the GAS muscles increased grip strength and muscle mass, leading to memory improvement in myostatin short-hairpin RNA-treated APP/PS1 mice. We conclude that high-level myostatin expression might mediate or trigger muscle atrophy and cognitive deficits.


Alzheimer’s disease Memory impairment APP/PS1 transgenic mice Myostatin 



We thank Dr. Shun-Hua Chen from the Department of Microbiology and Immunology, National Cheng Kung University, College of Medicine, for giving us APP/PS1 mice and Mr. Sung-En Chen for assisting in the behavioral experiments. We also thank Bill Franke, a native speaker of American English and technical editor, for proofreading the manuscript. This study was supported by grants MOST 105-2320-B-006-016 and MOST 106-2320-B-006-057-MY3 from the Taiwan Ministry of Science and Technology.

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Supplementary material

12035_2018_1201_Fig8_ESM.png (199 kb)
Supplementary Figure 1

Wet weights of tibialis anterior and triceps muscles in 12-month-old APP/PS1 mice. a Tibialis anterior muscle mass was lower in APP/PS1 mice (n = 9 in each group). ***p < 0.001 vs. age-matched WT controls. b Triceps muscle wet weights were not significantly different between age-matched WT controls and APP/PS1 mice (n = 9 in each group). (PNG 199 kb)

12035_2018_1201_MOESM1_ESM.tif (24.9 mb)
High resolution image (TIF 25501 kb)


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Authors and Affiliations

  1. 1.Department of Pharmacology, College of MedicineNational Cheng Kung UniversityTainanTaiwan
  2. 2.Institute of Basic Medical SciencesCollege of Medicine, National Cheng Kung UniversityTainanTaiwan
  3. 3.Institute of Behavioral MedicineCollege of Medicine, National Cheng Kung UniversityTainanTaiwan

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