Injection of β-amyloid into the hippocampus induces metabolic disturbances and involuntary weight loss which may be early indicators of Alzheimer's disease

摘要

Background: Alzheimer's disease (AD) and type 2 diabetes, two diseases that contribute considerable morbidity and mortality in middle-age and elderly people, coexist and progress in parallel, leading to the presumption that one may cause the other. However, a causative link has not yet been established. Methods: This study used non-diabetic and diabetic rats injected with β-amyloid (25-35) into the CA1 of the hippocampus to induce AD like plaques as a model of early-stage AD to evaluate the effects of AD on energy metabolism. AD like cognitive dysfunction was confirmed using passive avoidance tests and Morris water maze tests. Results: Diabetic and non-diabetic rats with experimental AD exhibited memory deficits by β-amyloid (25-35) accumulation in the hippocampus, but diabetes exacerbated memory impairment. All rats, diabetic and non-diabetic, infused with β-amyloid had profound decreases in energy intake, activity and fat oxidation and increased carbohydrate oxidation and energy expenditure. Energy expenditure was increased by 8-10% and energy intake decreased by approximately 20% in the rats injected with β-amyloid regardless of diabetic status. Conclusions: These results suggest that AD type plaques in the brain may induce metabolic disturbances and cachexia in early AD, which may be an early warning sign of AD in humans.