Background: Neurosteroids Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone
Sulphate (DHEAS) are involved in many important brain functions, including neuronal plasticity and
survival, cognition and behavior, demonstrating preventive and therapeutic potential in different neuropsychiatric
and neurodegenerative disorders, including Alzheimer’s disease.
Objective: The aim of the article was to provide a comprehensive overview of the literature on the involvement
of DHEA and DHEAS in Alzheimer’s disease.
Methods: PubMed and MEDLINE databases were searched for relevant literature. The articles were
selected considering their titles and abstracts. In the selected full texts, lists of references were searched
manually for additional articles.
Results: We performed a systematic review of the studies investigating the role of DHEA and DHEAS
in various in vitro and animal models, as well as in patients with Alzheimer’s disease, and provided a
comprehensive discussion on their potential preventive and therapeutic applications.
Conclusion: Despite mixed results, the findings of various preclinical studies are generally supportive
of the involvement of DHEA and DHEAS in the pathophysiology of Alzheimer’s disease, showing
some promise for potential benefits of these neurosteroids in the prevention and treatment. However, so
far small clinical trials brought little evidence to support their therapy in AD. Therefore, large-scale
human studies are needed to elucidate the specific effects of DHEA and DHEAS and their mechanisms
of action, prior to their applications in clinical practice.