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Clin Med Res. 2007 Oct;5(3):177-83.

The contribution of luteinizing hormone to Alzheimer disease pathogenesis.

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Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.


Several hypotheses have been proposed that attempt to explain the pathogenesis of Alzheimer Disease (AD) including theories involving senile plaque and neurofibrillary tangle formation, increased oxidative stress, and cell cycle abnormalities, since evidence for each of these pathological phenomena have been well documented in AD. Recent epidemiological and experimental data also support a role for the gonadotropin luteinizing hormone in AD. Paralleling the female predominance for developing AD, luteinizing hormone levels are significantly higher in females as compared to males, and furthermore, luteinizing hormone levels are higher still in individuals who succumb to AD. Luteinizing hormone, which is capable of modulating cognitive behavior, is not only present in the brain, but also has the highest receptor levels in the hippocampus, a key processor of cognition that is severely deteriorated in AD. Furthermore, we recently examined cognitive performance in a well-characterized transgenic mouse that over-expresses luteinizing hormone and found that these animals show decreased cognitive performance when compared to controls. We have also found that abolishing luteinizing hormone in amyloid-beta protein precursor transgenic mice (Tg2576) using a potent gonadotropin-lowering gonadotropin-releasing hormone agonist, leuprolide acetate, resulted in improved hippocampally-related cognitive performance and decreased amyloid-beta deposition. These findings, together with data indicating that luteinizing hormone modulates amyloid-beta protein precursor processing in vivo and in vitro, suggest that luteinizing hormone may contribute to AD pathology through an amyloid-dependent mechanism. These promising findings support the importance of luteinizing hormone in AD and bring to the forefront an alternative, and much needed, therapeutic avenue for the treatment of this insidious disease.

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