Obesity and Hepatic Steatosis Are Associated with Elevated Serum Amyloid Beta in Metabolically Stressed APPswe/PS1dE9 Mice

• Published in: PloS one Vol. 10; no. 8; p. e0134531
• Main Authors: Shie, Feng-Shiun, Shiao, Young-Ji, Yeh, Chih-Wen, Lin, Chien-Hung, Tzeng, Tsai-Teng, Hsu, Hao-Chieh, Huang, Fong-Lee, Tsay, Huey-Jen, Liu, Hui-Kang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.08.2015; Public Library of Science (PLoS)
• Subjects: Alzheimer's disease; Amyloid beta-Peptides - blood; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Analysis; Analysis of Variance; Animals; Blood Glucose - metabolism; Body weight; Body weight gain; Brain research; Care and treatment; Correlation analysis; Data processing; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - metabolism; Disease Models, Animal; Fatty Acids, Nonesterified - blood; Fatty liver; Fatty Liver - blood; Genetic engineering; Glucose; Glycoproteins; High fat diet; Humans; Hyperglycemia; Insulin resistance; Leptin - blood; Lipids - blood; Liver; Liver - metabolism; Liver - pathology; Male; Metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Obesity; Obesity - blood; Peptide Fragments - blood; Presenilin-1 - genetics; Presenilin-1 - metabolism; Risk factors; Rodents; Steatosis; Streptozocin; Stress, Physiological - genetics; Stresses; Transgenic mice; Triglycerides; Triglycerides - metabolism; Variance analysis; Weight Gain; β-Amyloid; United States > US; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0134531

Diabesity-associated metabolic stresses modulate the development of Alzheimer's disease (AD). For further insights into the underlying mechanisms, we examine whether the genetic background of APPswe/PS1dE9 at the prodromal stage of AD affects peripheral metabolism in the context of diabesity. We characterized APPswe/PS1dE9 transgenic mice treated with a combination of high-fat diet with streptozotocin (HFSTZ) in the early stage of AD. HFSTZ-treated APPswe/PS1dE9 transgenic mice exhibited worse metabolic stresses related to diabesity, while serum β-amyloid levels were elevated and hepatic steatosis became apparent. Importantly, two-way analysis of variance shows a significant interaction between HFSTZ and genetic background of AD, indicating that APPswe/PS1dE9 transgenic mice are more vulnerable to HFSTZ treatment. In addition, body weight gain, high hepatic triglyceride, and hyperglycemia were positively associated with serum β-amyloid, as validated by Pearson's correlation analysis. Our data suggests that the interplay between genetic background of AD and HFSTZ-induced metabolic stresses contributes to the development of obesity and hepatic steatosis. Alleviating metabolic stresses including dysglycemia, obesity, and hepatic steatosis could be critical to prevent peripheral β-amyloid accumulation at the early stage of AD.