Alzheimer’s disease (AD) is a devastating neurodegenerative disorder, most notably associated with memory deficits and cognitive impairment. Despite extensive research, there remains an urgent need to develop disease-modifying therapies that may slow the progression of AD. Late-life depression has emerged as a significant risk factor for AD. Genome-wide association studies have indicated that the genetic risk for depression may contribute to the development of AD, whereas AD genetic risk does not reciprocally increase the risk of depression. Shared molecular features between AD and depression, such as disturbances in cholinergic/serotonergic neurotransmission and the hypothalamic-pituitary-adrenal (HPA) axis, warrant further exploration.

The primary goal of this Research Topic is to elucidate how depression contributes to cognitive decline both before and within the context of AD, at molecular and cellular levels. Antidepressant drugs, particularly selective serotonin reuptake inhibitors (SSRIs), have shown promise in improving cognitive and memory functions and reducing amyloid pathologies in AD models. However, short-term use of SSRIs may paradoxically increase the risk of dementia. Understanding the detailed mechanisms by which antidepressants influence cognitive function and amyloid pathology is crucial for developing new drugs that can improve cognitive functions without exacerbating dementia risk. We aim to identify and characterize these mechanisms, thereby facilitating the development of safer and more effective therapeutic strategies for AD.

We welcome research articles that delve into the precise molecular and cellular mechanisms of action of approved or investigational antidepressant drugs in the context of AD.
Submissions could address, but are not limited to, the following themes:

• Molecular pathways linking depression to cognitive decline in AD
• Mechanisms of action of SSRIs and other antidepressants on cholinergic/serotonergic neurotransmission in AD
• Role of the HPA axis in mediating the effects of antidepressants in AD
• Identification of novel drug targets for the treatment of depression that improve cognitive function without increasing dementia risk

We welcome various types of manuscripts, including original research articles, reviews, and short communications focused on investigative and therapeutic perspectives related to antidepressants and AD.

Dr. Jinseol Rhee is a Stockholder of Aribio Co., Ltd. in South Korea. The other Topic Editors report no competing interests related to this Research Topic.

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Exploring the Intersection of Depression and Alzheimer’s: Mechanisms and Therapeutic Strategies