An Association of Elevated Serum Gonadotropin Concentrations and Alzheimer Disease?

Bowen,; Isley,; Atkinson, Joanna

doi:10.1046/j.1365-2826.2000.00461.x

Cited by 147 publications

(112 citation statements)

References 32 publications

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“…57,58 Since gonadotropin receptors in the brain are found within the hippocampus 59 and gonadotropins are known to cross the blood brain barrier, 60 we speculate that elevated gonadotropins, namely LH, may contribute to AD pathogenesis. 57 In support of this theory, we found significant elevations of LH in vulnerable neuronal populations in individuals with AD compared to age-matched control cases. 61 Notably, such an increase in neuronal LH appears to be a very early change in disease progression serving to predict neuronal populations at risk of degeneration and death.…”

Section: Luteinizing Hormone In Alzheimer Diseasementioning

confidence: 94%

The Contribution of Luteinizing Hormone to Alzheimer Disease Pathogenesis

Webber¹,

Perry²,

Smith³

et al. 2007

Clinical Medicine & Research

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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...

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Section: Luteinizing Hormone In Alzheimer Diseasementioning

confidence: 94%

The Contribution of Luteinizing Hormone to Alzheimer Disease Pathogenesis

Webber¹,

Perry²,

Smith³

et al. 2007

Clinical Medicine & Research

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“…Both serum E2 and T levels were lower in men with AD compared to age-matched controls. 191,192 E2 could exert protective effects on the brain structures in aging patients. 193 Trials of testosterone therapy in men to evaluate its effects on measures of cognitive function and memory to date were all relatively small and of a relatively short duration and have shown mixed results.…”

Section: Cognitive Functionmentioning

confidence: 99%

The benefits and risks of testosterone replacement therapy: a review

Bassil¹,

Alkaade²,

Morley

2009

TCRM

145

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“…AD is the most common form of clinical dementia and is characterized by selective neurodegeneration in the hippocampus and progressive memory loss leading to cognitive decline. Reports find serum LH to be significantly higher in individuals with AD compared to age matched controls (Bowen et al, 2000;Short et al, 2001;Hogervorst et al, 2004; though for contradictory evidence see Hogervorst et al, 2003). Patients with Down syndrome have elevated levels of LH throughout life and develop cognitive impairment and AD-like lesions early in life (Mann, 1988;Oliver and Holland, 1986).…”

Section: Introductionmentioning

confidence: 98%

Human chorionic gonadotropin (a luteinizing hormone homologue) decreases spatial memory and increases brain amyloid-β levels in female rats

Berry

Tomidokoro

Ghiso

et al. 2008

Hormones and Behavior

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Numerous studies have suggested that estradiol (E) improves spatial memory as female rats with E perform better than those without E. However there is an inverse relationship between E and luteinizing hormone (LH) levels and LH could play a role. We examined whether treatment with the LH homologue human chorionic gonadotropin (hCG), would impair spatial memory of adult Etreated female rats. In the Object Location Memory Task, ovariectomized (ovxed) rats treated with E and either a single high dose (400IU/kg) or a lower repeated dose of hCG (75 IU/kg hourly for 8 hours) showed spatial memory disruption compared to ovxed rats treated with estradiol alone. Impairment was attributed to memory disruption as performance improved with shortened delay between task exposure and testing. Tests on another spatial memory task, the Barnes maze, confirmed that hCG (400IU/kg) can impair memory: although E + veh treated animals made significantly fewer hole errors across time, E + hCG treated did not. In humans, high LH levels have been correlated with Alzheimer's Disease (AD). Because brain amyloid-beta (Aβ) species have been implicated as a toxic factor thought to cause memory loss in AD, we analyzed whether hCG-treated animals had increased Aβ levels. Levels of Aβ from whole brains or hippocampi were assessed by Western Blot. hCG treatment to E-implanted females significantly increased soluble Aβ40 and Aβ42 levels. These results indicate that high levels of LH/hCG can impair spatial memory, and an increase in brain Aβ species may account for the memory impairment in hCG-treated rats.

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An Association of Elevated Serum Gonadotropin Concentrations and Alzheimer Disease?

Cited by 147 publications

References 32 publications

The Contribution of Luteinizing Hormone to Alzheimer Disease Pathogenesis

The Contribution of Luteinizing Hormone to Alzheimer Disease Pathogenesis

The benefits and risks of testosterone replacement therapy: a review

Human chorionic gonadotropin (a luteinizing hormone homologue) decreases spatial memory and increases brain amyloid-β levels in female rats

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