Perspectives on the Implications of Depression on Alzheimer’s Disease: Shared Pathophysiology, Epidemiological Challenges and Therapeutic Management

Alzheimer’s disease (AD) and depression are interrelated neuropsychiatric disorders that share underlying mechanisms such as neuroinflammation, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, and imbalances in neurotransmitters. This review analyses the reciprocal relationship between AD and depression, emphasising standard pathological mechanisms, epidemiological patterns, preclinical models and emerging treatment strategies. A structured narrative review of the literature was performed using PubMed, Scopus and Web of Science. Articles published between 2000 and 2025 were chosen based on their relevance to animal models and therapeutic approaches connecting AD and depression. Depression significantly raises the likelihood of developing AD, while the progression of AD exacerbates depressive symptoms. Standard mechanisms involve increased levels of Interleukin-6 (IL-6) and Tumour Necrosis Factor Alpha (TNF-α), decreased brain-derived neurotrophic factor (BDNF) and disruptions in the HPA axis. Therapeutic strategies targeting inflammation and neuroendocrine regulation have shown encouraging outcomes. A comprehensive understanding of the overlapping pathophysiology of AD and depression is crucial for early identification and effective treatment. Future investigations should focus on biomarker-driven diagnostics, modulation of the gut-brain axis, and personalised treatment options.