Type 2 Diabetes and Alzheimer's Disease: The Emerging Role of Cellular Lipotoxicity

Type 2 diabetes (T2D) and Alzheimer's diseases (AD) represent major health issues that have reached alarming levels in the last decades. Although growing evidence demonstrates that AD is a significant comorbidity of T2D, and there is a similar to 1.4-2-fold increase in the risk of developing AD among T2D patients, the involvement of possible common triggers in the pathogenesis of these two diseases remains largely unknown. Of note, recent mechanistic insights suggest that lipotoxicity could represent the missing ring in the pathogenetic mechanisms linking T2D to AD. Indeed, obesity, which represents the main cause of lipotoxicity, has been recognized as a major risk factor for both pathological conditions. Lipotoxicity can lead to inflammation, insulin resistance, oxidative stress, ceramide and amyloid accumulation, endoplasmic reticulum stress, ferroptosis, and autophagy, which are shared biological events in the pathogenesis of T2D and AD. In the current review, we try to provide a critical and comprehensive view of the common molecular pathways activated by lipotoxicity in T2D and AD, attempting to summarize how these mechanisms can drive future research and open the way to new therapeutic perspectives.

Automated summary

Type 2 diabetes and Alzheimer's disease are major health issues with a close relationship. Lipotoxicity may be the missing link connecting the pathogenesis of these two diseases. Obesity, the main cause of lipotoxicity, is a major risk factor for both conditions. This review provides a comprehensive overview of the common molecular pathways activated by lipotoxicity in type 2 diabetes and Alzheimer's disease, suggesting potential new therapeutic perspectives.