Beyond estrogen: targeting gonadotropin hormones in the treatment of Alzheimer's disease

Current Drug Targets. CNS and Neurological Disorders
Gemma CasadesusMark A Smith

Abstract

Based on epidemiological and observational studies, estrogen and hormone-replacement therapy were until recently viewed as major factors in the prevention of Alzheimer's disease (AD). However, a recent randomized clinical trial revealed that hormone replacement therapy using estrogen plus progestin may actually exacerbate the incidence of dementia when administered to elderly women. These contradictory reports have cast grave doubt on the role of estrogen in disease pathogenesis and led us to consider an alternate hypothesis that would be consistent with both observations. Specifically, we suspect that hormones of the hypothalamic pituitary gonadal axis such as gonadotropins, that are regulated by estrogen (or in males by testosterone), are involved in the pathogenesis of Alzheimer's disease. One such gonadotropin, luteinizing hormone (LH), is significantly elevated in both the sera and brain tissue of patients with AD and leads to an increased production of amyloid-beta. Importantly, a key role in disease pathogenesis is further supported by the fact that the distribution of neuronal receptors for LH parallels those populations of neurons that degenerate during the course of the disease. That gonadotropins, not estrogen nor te...Continue Reading

Citations

Jun 7, 2005·Mechanisms of Ageing and Development·Kate M WebberMark A Smith
May 12, 2007·Expert Review of Neurotherapeutics·Rudy J CastellaniMark A Smith
Mar 23, 2007·Molecular and Cellular Endocrinology·Gemma CasadesusMark A Smith
Aug 30, 2007·Journal of Peptide Science : an Official Publication of the European Peptide Society·Reyhaneh AstanehMohammad Erfan
Oct 21, 2006·Molecular and Cellular Endocrinology·Kate M WebberMark A Smith
Mar 1, 2006·Biochimica Et Biophysica Acta·Gemma CasadesusMark A Smith

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