Metabolic perspective of astrocyte dysfunction in Alzheimer's disease and type 2 diabetes brains

The term type III diabetes (T3DM) has been proposed for Alzheimer's disease (AD) due to the shared molecular and cellular features between type 2 diabetes (T2DM) and insulin resistance-associated memory deficits and cognitive decline in elderly individuals. Astrocytes elicit neuroprotective or deleterious effects in AD progression and severity. Patients with T2DM are at a high risk of cognitive impairment, and targeting astrocytes might be promising in alleviating neurodegeneration in the diabetic brain. Recent studies focusing on cell-specific ac-tivities in the brain have revealed the important role of astrocytes in brain metabolism (e.g., glucose metabolism, lipid metabolism), neurovascular coupling, synapses, and synaptic plasticity. In this review, we discuss how astrocytes and their dysfunction result in multiple pathological and clinical features of AD and T2DM from a metabolic perspective and the potential comorbid mechanism in these two diseases from the perspective of astrocytes.

Automated summary

The term type III diabetes (T3DM) is proposed for Alzheimer's disease (AD) due to similarities in molecular and cellular features with type 2 diabetes (T2DM). Astrocytes play a crucial role in AD progression and severity, and targeting them could help alleviate neurodegeneration in the diabetic brain. Recent studies have shown the significant role of astrocytes in brain metabolism, neurovascular coupling, synapses, and synaptic plasticity. This review discusses how astrocyte dysfunction contributes to the pathological and clinical features of AD and T2DM from a metabolic perspective.