Luteinizing hormone as a key player in the cognitive decline of Alzheimer's disease

• Luteinizing hormone (LH) increases with aging and is associated with Alzheimer's disease in humans.
• LH causes cognitive decline in animal models.
• LH is associated with Alzheimer's disease pathology.
• Downregulation of LH may serve as an effective treatment for Alzheimer's disease.

This article is part of a Special Issue "SBN 2014".Alzheimer's disease is one of the most prevalent and costly neurological diseases in the world. Although decades of research have focused on understanding Alzheimer's disease pathology and progression, there is still a great lack of clinical treatments for those who suffer from it. One of the factors most commonly associated with the onset of Alzheimer's disease is a decrease in levels of gonadal hormones, such as estrogens and androgens. Despite the correlational and experimental data which support the role of these hormones in the etiology of Alzheimer's disease, clinical trials involving their reintroduction through hormone therapy have had varied results and these gonadal hormones often have accompanying health risks. More recently, investigation has turned toward other hormones in the hypothalamic–pituitary–gonadal axis that are disrupted by age-related decreases in gonadal hormones. Specifically, luteinizing hormone, which is increased with age in both men and women (in response to removal of negative feedback), has surfaced as a potentially powerful player in the risk and onset of Alzheimer's disease. Mounting evidence in basic research and epidemiological studies supports the role of elevated luteinizing hormone in exacerbating age-related cognitive decline in both males and females. This review summarizes the recent developments involving luteinizing hormone in increasing the cognitive deficits and molecular pathology characteristic of Alzheimer's disease.