The Crossroads of Neurodegeneration: Exploring the Overlap Between Alzheimer's Disease and Depression

Alzheimer's disease (AD) and depression are two prevalent and debilitating neuropsychiatric disorders that frequently occur together and share overlapping clinical and molecular features. Understanding shared features of AD and depression is critical for delaying disease progression and improving quality of life. The objective of this narrative review is to identify recent advances in the understanding of AD and its link to depression, with a focus on identifiable biomarkers. This review explores the converging pathophysiological pathways implicated in both AD and depression, with an emphasis on oxidative stress, mitochondrial dysfunction, microglial activation, vascular impairment, and metal ion dysregulation. Specific attention is given to biomarkers of lipid peroxidation, nucleic acid damage, and protein nitration, as well as to the role of telomerase activity and ferroptosis in neuronal cell death. Additionally, we evaluate the therapeutic potential of antidepressants in modifying disease trajectory and reducing depressive symptoms in AD patients. By investigating the molecular intersections of AD and depression, this review aims to provide a comprehensive understanding of their shared pathology and highlight new avenues for targeted interventions. Our review underscores the overlapping mechanisms between AD and depression, paving the way for earlier detection, targeted therapies, closer monitoring, and improved patient outcomes.