The Contribution of Luteinizing Hormone to Alzheimer Disease Pathogenesis

Abstract

Al zheimer Disease (AD) is the most prevalent neurodegenerative disease affecting more than 15 million people worldwide 1 and is characterized by selective neuronal degeneration resulting in progressive memory loss. 2 AD attacks several different regions of the brain including the cerebral cortex which is involved in conscious thought and language, the basal forebrain which is important in memory and learning, and the hippocampus which is essential to memory storage. Clinical manifestations of AD are varied but can include memory loss, difficulty performing familiar tasks, disorientation to time and place, misplacing things, and changes in mood or behavior. 3 Several hypotheses have been proposed in attempts to explain the pathogenesis of AD and include 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. 4 The senile plaque, which is primarily composed of the 4.2 kDa amyloid-β polypeptide, is produced from the proteolytic cleavage of the larger amyloid-β precursor protein (AβPP) and is the extracellular hallmark of AD. To date, three genes involving AβPP or its cleavage product have been identified as containing fully penetrant, mutations resulting in early-onset AD. These mutations can be found on genes encoding AβPP itself and also on presenilin-1 and presenilin-2 genes. 5 While these mutations are known to 177 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-β 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-β deposition. These findings, together with data indicating that luteinizing hormone modulates amyloid-β protein precursor p...

Hemolytic E. coli Promotes Colonic Tumorigenesis in Females

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“…It is beyond the scope of this study but warrants further investigation why females are more vulnerable to colorectal cancer carcinogenesis mediated by hemolytic type I E. coli. Gender-dependent differences have been known to exist in the etiology and pathogenesis of a long list of diseases such as heart failure (39), viral infections (40), and Alzheimer disease (41). Mechanisms underlying the gender difference remain poorly understood and may involve complex processes.…”

Luteinizing-hormone Releasing Hormone Therapy and the Risk of Death From Alzheimer Disease

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Androgens and Alzheimer's disease

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