Elevated Gonadotropin Levels in Patients With Alzheimer Disease

Short, Rodney A.; O’Brien, Peter C.; Graff‐Radford, Neill R.; Bowen, Richard L.

doi:10.1016/s0025-6196(11)62109-5

Cited by 121 publications

(39 citation statements)

References 14 publications

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“…Epidemiological data demonstrate that patients with AD have higher levels of LH than do individuals who do not develop the disease [35,36]. Moreover, in addition to explaining the therapeutic controversies associated with HRT and dementia, increasing LH levels can also explain the higher predominance for developing AD in females when compared to males [37][38][39][40][41].…”

Section: Elevations In Lh Are Associated With Ad Pathologymentioning

confidence: 99%

Alzheimer?s disease: the impact of age-related changes in reproductive hormones

Casadesús

Atwood

Zhu

et al. 2005

CMLS, Cell. Mol. Life Sci.

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Differences in the prevalence and age of onset of Alzheimer disease (AD) in men and women, and observations that hormone replacement therapy (HRT) may prevent the development of AD, caused many to hypothesize that estrogen deficiency contributes to AD. However, recent trials using estrogen failed to show any benefit in preventing or alleviating the disease. To address this and other inconsistencies in the estrogen hypothesis, we suspect that another hormone of the hypothalamic-pituitary-gonadal axis, luteinizing hormone (LH), as a major factor in AD pathogenesis. Individuals with AD have elevated levels of LH when compared with controls, and both LH and its receptor are present in increased quantities in brain regions susceptible to degeneration in AD. LH is also known to be mitogenic, and could therefore initiate the cell cycle abnormalities known to be present in AD-affected neurons. In cell culture, LH increases amyloidogenic processing of amyloid-beta protein precursor, and in animal models of AD, pharmacologic suppression of LH and FSH reduces plaque formation. Given the evidence supporting a pathogenic role for LH in AD, a trial of leuprolide acetate, which suppresses LH release, has been initiated in patients.

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Section: Elevations In Lh Are Associated With Ad Pathologymentioning

confidence: 99%

Alzheimer?s disease: the impact of age-related changes in reproductive hormones

Casadesús

Atwood

Zhu

et al. 2005

CMLS, Cell. Mol. Life Sci.

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show abstract

“…The gonadotropins have also been implicated in the pathogenesis of AD. Previous reports have shown in a small cohort that the serum levels of gonadotropins are higher in AD patients compared to age-matched controls (Bowen et al, 2000), (Short et al, 2001).…”

Section: The Role Of Gonadotropins In Ad Risk and Pathogenesismentioning

confidence: 77%

The impact of luteinizing hormone and testosterone on beta amyloid (Aβ) accumulation: Animal and human clinical studies

Verdile

Asih

Barron³

et al. 2015

Hormones and Behavior

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“…[20]. LH levels also were significantly higher in estrogen-free female AD patients compared to female frontotemporal patients: (26.3 IU/L vs. 20.7 IU/L) (p = 0.0286).…”

Section: Evidence Supporting a Role For Gonadotropins In Admentioning

confidence: 84%

“…Signed rank tests on the resulting 38 pairs were statistically significant for LH (p = 0.048), but not for FSH (p = 0.342) [20]. In contrast, Mayeux and colleagues saw no significant difference in serum gonadotropin concentrations between control and AD females [21].…”

Section: Evidence Supporting a Role For Gonadotropins In Admentioning

confidence: 88%

Alzheimer?s disease: the impact of age-related changes in reproductive hormones

Gregory

Bowen

2005

CMLS, Cell. Mol. Life Sci.

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The relationship between hormones and Alzheimer's disease (AD) has been intensely researched. While the majority of this work has focused on the sex steroids, estrogens, and more recently androgens, a serendipitous patient encounter led one of us (R.L.B.) to question whether other hormones of the hypothalamic-pituitary-gonadal axis might play a role in the pathogenesis of AD. The age-related decline in reproductive function results in a dramatic decrease in serum estrogen and testosterone concentrations and an equally dramatic compensatory increase in serum gonadotropin concentrations. Indeed, there is growing evidence that the gonadotropin luteinizing hormone, which regulates serum estrogen and testosterone concentrations, is an important causative factor in the development of AD. This review provides information supporting the 'gonadotropin hypothesis'. We put forth a novel mechanism of how changes in serum luteinizing hormone concentrations could contribute to the pathogenesis of AD and discusses potential therapeutic anti-gonadotropin compounds.

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Elevated Gonadotropin Levels in Patients With Alzheimer Disease

Cited by 121 publications

References 14 publications

Alzheimer?s disease: the impact of age-related changes in reproductive hormones

Alzheimer?s disease: the impact of age-related changes in reproductive hormones

The impact of luteinizing hormone and testosterone on beta amyloid (Aβ) accumulation: Animal and human clinical studies

Alzheimer?s disease: the impact of age-related changes in reproductive hormones

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