Metabolic Syndrome as a Risk Factor for Alzheimer's Disease: Is Aβ a Crucial Factor in Both Pathologies?

SIGNIFICANCE: Recently, chronic degenerative diseases have become one of the main health problems worldwide. That is the case of Alzheimer's disease (AD) and metabolic syndrome (MetS), whose expression can be influenced by different risk factors. Recent Advances: In recent decades, it has been widely described that MetS increases the risk of cognitive impairment and dementia. MetS pathogenesis involves several vascular risk factors such as diabetes, dyslipidemia, hypertension, and insulin resistance (I/R). CRITICAL ISSUES: Reported evidence shows that vascular risk factors are associated with AD, particularly in the development of protein aggregation, inflammation, oxidative stress, neuronal dysfunction, and disturbances in signaling pathways, with insulin receptor signaling being a common alteration between MetS and AD. FUTURE DIRECTIONS: Insulin signaling has been involved in tau phosphorylation and amyloid β (Aβ) metabolism. However, it has also been demonstrated that Aβ oligomers can bind to insulin receptors, triggering their internalization, decreasing neuron responsiveness to insulin, and promoting insulin I/R. Thus, it could be argued that Aβ could be a convergent factor in the development of both pathologies. Antioxid. Redox Signal. 26, 542-560.