Gender differences in Alzheimer disease: the role of luteinizing hormone in disease pathogenesis.
Epidemiological data reporting the predisposition of women to Alzheimer disease has provided researchers with an important clue as to the identity of the driving pathogenic force and lead many to question the potential role of sex steroids, namely estrogen, in disease pathogenesis. However, while estrogen has become the primary focus of research in the field, inconclusive data regarding estrogen replacement therapy has lead some researchers to begin investigating the effects of the other hormones of the hypothalamic-pituitary-gonadal (HPG) axis on the aging brain. Certain hormones of the HPG axis, namely the gonadotropins (luteinizing hormone and follicle-stimulating hormone), are not only involved in regulating reproductive function via a complex feedback loop but are also known to cross the blood-brain barrier. Recently, we proposed that an increase in gonadotropin concentrations, not the decrease in steroid hormone (eg, estrogen) production following menopause/andropause, is a potentially primary causative factor for the development of Alzheimer disease. In this review, we examine how the gonadotropins may play a central and determining role in modulating the susceptibility to, and progression of, Alzheimer disease. Based on this, we suggest that therapeutic interventions targeted at gonadotropins may both prevent disease in those patients currently asymptomatic or may halt, and even reverse, disease in those currently afflicted.
Webber
Kate M
KM
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Casadesus
Gemma
G
Perry
George
G
Atwood
Craig S
CS
Bowen
Richard
R
Smith
Mark A
MA
D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D000818:Animals; D006727:Hormone Antagonists / Q000627:therapeutic use; D006801:Humans; D007986:Luteinizing Hormone / Q000502:physiology*; D012727:Sex Characteristics
D006727:Hormone Antagonists; D007986:Luteinizing Hormone