Endogenous estrogen levels and Alzheimer’s disease among postmenopausal women

Manly, Jennifer J.; Merchant, Carol; Jacobs, Diane M.; Small, Scott A.; Bell, Karen L.; Ferin, Michel; Mayeux, Richard

doi:10.1212/wnl.54.4.833

Cited by 222 publications

(139 citation statements)

References 42 publications

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“…Some studies have not shown significant differences between healthy women and women with AD (Cunningham et al, 2001). On the contrary, other studies have found decreased levels of estradiol in AD patients (Manly et al, 2000). One study has reported decreased estradiol levels in the cerebrospinal fluid of AD patients and a negative correlation with ␤-amyloid levels (Schonknecht et al, 2001).…”

Section: Steroidal Aging In Humansmentioning

confidence: 93%

Steroid hormones and neurosteroids in normal and pathological aging of the nervous system

Schumacher

Weill-Engerer

Lière

et al. 2003

Progress in Neurobiology

272

171

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Without medical progress, dementing diseases such as Alzheimer's disease will become one of the main causes of disability. Preventing or delaying them has thus become a real challenge for biomedical research. Steroids offer interesting therapeutical opportunities for promoting successful aging because of their pleiotropic effects in the nervous system: they regulate main neurotransmitter systems, promote the viability of neurons, play an important role in myelination and influence cognitive processes, in particular learning and memory. Preclinical research has provided evidence that the normally aging nervous system maintains some capacity for regeneration and that age-dependent changes in the nervous system and cognitive dysfunctions can be reversed to some extent by the administration of steroids. The aging nervous system also remains sensitive to the neuroprotective effects of steroids. In contrast to the large number of studies documenting beneficial effects of steroids on the nervous system in young and aged animals, the results from hormone replacement studies in the elderly are so far not conclusive. There is also little information concerning changes of steroid levels in the aging human brain. As steroids present in nervous tissues originate from the endocrine glands (steroid hormones) and from local synthesis (neurosteroids), changes in blood levels of steroids with age do not necessarily reflect changes in their brain levels. There is indeed strong evidence that neurosteroids are also synthesized in human brain and peripheral nerves. The development of a very sensitive and precise method for the analysis of steroids by gas chromatography/mass spectrometry (GC/MS) offers new possibilities for the study of neurosteroids. The concentrations of a range of neurosteroids have recently been measured in various brain regions of aged Alzheimer's disease patients and aged non-demented controls by GC/MS, providing reference values. In Alzheimer's patients, there was a general trend toward lower levels of neurosteroids in different brain regions, and neurosteroid levels were negatively correlated with two biochemical markers of Alzheimer's disease, the phosphorylated tau protein and the ␤-amyloid peptides. The metabolism of dehydroepiandrosterone has also been analyzed for the first time in the aging brain from Alzheimer patients and non-demented controls. The conversion of dehydroepiandrosterone to 5-androstene-3␤,17␤-diol and to 7␣-OH-dehydroepiandrosterone occurred in frontal cortex, hippocampus, amygdala, cerebellum and striatum of both Alzheimer's patients and controls. The formation of these metabolites within distinct brain regions negatively correlated with the density of ␤-amyloid deposits.

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Section: Steroidal Aging In Humansmentioning

confidence: 93%

Steroid hormones and neurosteroids in normal and pathological aging of the nervous system

Schumacher

Weill-Engerer

Lière

et al. 2003

Progress in Neurobiology

272

171

View full text Add to dashboard Cite

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“…In fact, it is long known that women experience a sharp increase in the risk of developing AD after menopause [65,103]. This is further strengthened by the fact that ovariectomy promotes the amyloidogenic processing of APP [76,122,166,175], and that these effects are partially or totally reverted by estrogen treatment [122,175].…”

Section: Igf1-r Neurotrophin Signaling and Ad: A Tale Of Receptors mentioning

confidence: 99%

Aging of the brain, neurotrophin signaling, and Alzheimer's disease: Is IGF1-R the common culprit?

Puglielli¹

2008

Neurobiology of Aging

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The last decade has revealed that the lifespan of an organism can be modulated by the signaling pathway that acts downstream of the insulin/insulin-like growth factor 1 receptors (IR/IGF1-R), indicating that there is a "program" that drives the process of aging. New results have now linked the same pathway to the neurogenic capacities of the aging brain, to neurotrophin signaling, and to the molecular pathogenesis of Alzheimer's disease. Therefore, a common signaling cascade now seems to link aging to age-associated pathologies of the brain, suggesting that pharmacologic approaches aimed at the modulation of this pathway can serve to delay the onset of age-associated disorders and improve the quality of life. Work from a wide range of fields performed with different approaches has already identified some of the signaling molecules that act downstream of IGF1-R, and has revealed that a delicate checkpoint exists to balance excessive growth/"immortality" and reduced growth/"senescence" of a cell. Future research will determine how far the connection goes and how much of it we can influence.

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“…Relatively low estradiol levels in the late postmenopause have been linked to Alzheimer's disease risk in women (Manly et al, 2000;Hoskin et al, 2004), but again there are inconsistencies (Geerlings et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Hormone levels and cognitive function in postmenopausal midlife women

Ryan

Stanczyk

Dennerstein

et al. 2012

Neurobiology of Aging

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Gonadal hormones may influence cognitive function. Postmenopausal midlife women in the populationbased Melbourne Women's Midlife Health Project cohort were administered a comprehensive battery of neuropsychological tests on two occasions two years apart. Participants (n=148, mean age 60 years) had undergone natural menopause and were not using hormone therapy. Estrone, total and free estradiol, and total and free testosterone levels were measured at time of the first testing. Principal component analysis identified four cognitive factors. In multiple linear regression analyses, better semantic memory performance was associated with higher total (p=0.02) and free (p=0.03) estradiol levels and a lower ratio of testosterone to estradiol (p=0.007). There were trends for associations between better verbal episodic memory and lower total testosterone (p=0.08) and lower testosterone/estradiol ratio (p=0.06). Lower free testosterone levels were associated with greater two-year improvement on verbal episodic memory (p=0.04); higher testosterone/estradiol predicted greater semantic memory improvement (p=0.03). In postmenopausal midlife women, endogenous estradiol and testosterone levels and the testosterone/estradiol ratio are associated with semantic memory and verbal episodic memory abilities.

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Endogenous estrogen levels and Alzheimer’s disease among postmenopausal women

Abstract: The results of this preliminary case-control study suggest that estradiol levels may decline significantly in women in whom AD develops.

Cited by 222 publications

References 42 publications

Steroid hormones and neurosteroids in normal and pathological aging of the nervous system

Steroid hormones and neurosteroids in normal and pathological aging of the nervous system

Aging of the brain, neurotrophin signaling, and Alzheimer's disease: Is IGF1-R the common culprit?

Hormone levels and cognitive function in postmenopausal midlife women

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