Alzheimer’s disease (AD) is the sixth leading cause of death and is correlated with obesity, which is the second leading cause of preventable diseases in the United States. Obesity, diabetes, and AD share several common features, and inflammation emerges as the central link. High-calorie intake, elevated free fatty acids, and impaired endocrine function leads to insulin resistance and systemic inflammation. Systemic inflammation triggers neuro-inflammation, which eventually hinders the metabolic and regulatory function of the brain mitochondria leading to neuronal damage and subsequent AD-related cognitive decline. As an early event in the pathogenesis of AD, chronic inflammation could be considered as a potential biomarker in the treatment strategies for AD.