Creatine Supplementation Increases Muscle Branched‐Chain Amino Acids in an Alzheimer Mouse Model

Abstract

Besides mental dysfunctions, Alzheimer's disease (AD) may impair muscle function. Creatine supplementation (CR) can enhance skeletal muscle mass and function in sarcopenia and muscular dystrophies, but has yet to be studied in AD. We examined the effect of oral CR on muscle amino acids (AA) level in an AD model.24 triple transgenic (3×Tg, ~8 mo old) AD mice were randomly assigned to control (CON; 6 males (M)/6 females (F)) or CR (3% w/w; 4M/8F) diet. Bodyweights and feed intakes were measured throughout the 8‐week study. Quadriceps muscle (QM) was collected at the end to analyze for levels of creatine and AA and measured by high‐performance liquid‐chromatography. Data (mean±SEM) were analyzed by 2‐way ANOVAs.Feed intakes and changes in bodyweight were similar among groups (p>0.05). Creatine content in QM was higher (p=0.067) in CR (M: 0.38±0.04, F: 0.38±0.02 nmol/μl) vs. CON (M: 0.33±0.01, F: 0.35±0.01 nmol/μl). Total branched‐chain AA (BCAA) level in QM was greater for CR (M: 111.10±8.51, F: 87.26±4.31 nmol/mg tissue) vs. CON (M: 78.56±4.46, F: 66.07±4.35 nmol/mg tissue). BCAA/non‐BCAA ratio was higher (p=0.002) in CR (M: 0.87±0.17, F: 0.58±0.03) vs. CON (M: 0.54±0.04, F: 0.45±0.03). Particularly, leucine was dramatically increased (p<0.0001) in CR (M: 61.15±5.64, F: 47.28±2.55 nmol/mg) vs. CON (M: 34.21±2.64, F: 25.49±2.38 nmol/mg).CR supplementation enhances muscle AA contents, increasing BCAA levels in the 3×Tg AD mouse model, which may promote muscle function in AD.Funded by CIHR and Everett Endowment Fund