Neuroglial Crosstalk in Alzheimer's Disease and Diabetes Mellitus: Unravelling Shared Pathophysiological Pathways and Therapeutic Insights

Alzheimer's disease and type 2 diabetes mellitus are two of the most important global public health issues. While historically regarded in the context of distinct clinical and pathological entities, the latest evidence promises an enormous pathophysiological overlap between these conditions—based on the dysfunction of neuroglial cells. Microglia, astrocytes, and oligodendrocytes, all of which play crucial functions in immune surveillance, metabolic regulation, and synaptic homeostasis of the central nervous system, undergo revolutionary alterations in both Alzheimer's Disease (AD) and Type 2 Diabetes (T2D). These alterations include chronic low-grade inflammation, insulin resistance, mitochondrial damage, oxidative stress, and maladaptive intercellular communication—fostering an environment favourable to neurodegeneration and cognitive impairment.In this review we shed light on the interconnected and convergent functions of glial cells in AD and T2D pathophysiology, emphasizing the shared cellular mechanisms that bind these conditions. We address how glial metabolic reorganization, inflammasome activation, and disrupted neuroglial crosstalk drive disease progression. We also talk about therapeutic strategies that address glial dysfunction, such as anti-inflammatory medications, metabolic modulators, and precision medicine strategies that aim at glial subtype-selective vulnerabilities.By re-prioritizing glial cells as central players in the pathologies of both AD and T2D, this article fosters a more holistic understanding and treatment of these diseases. Restoration of glial homeostasis offers a promising avenue for early intervention, neuroprotection, and disease modification in the age in which metabolic and cognitive well-being are inextricably intertwined.