Age and sex differences of dehydroepiandrosterone sulfate (DHEAS) and cortisol (CRT) plasma levels in normal controls and Alzheimer's disease (AD)

Leblhuber, Friedrich; Neubauer, C.; Peichl, Marianne; Reisecker, F; Steinparz, F.X.; Windhager, Elmar; Dienstl, E

doi:10.1007/bf02257402

Cited by 55 publications

(18 citation statements)

References 26 publications

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“…Recent studies suggested that DHEA-S may increase some cerebral acetylcholinergic-dependent functions and that its decline may be associated with a greater susceptibility to the damage from neuroexcitatory aminoacids (Rhodes et al, 1997;Kimonides et al, 1998). The evidence of an association between DHEA-S levels and dementia is much less definite in humans, and most studies on small series of patients including different subtypes of dementia reported conflicting results (Cuckle et al, 1990;Spath-Schwalbe et al, 1990;Schneider et al, 1992;Leblhuber et al, 1993;Barret-Connor and Edelstein, 1994;Legrain et al, 1995;Berr et al, 1996;Yaffe et al, 1998;Wolf et al, 1999;Hillen et al, 2000). Findings of the present study do not show a significant association between DHEA-S levels and DAT.…”

Section: Discussionmentioning

confidence: 93%

“…In a small case-control study, Sunderland et al (1989) observed lower DHEA levels in early Alzheimer's disease than in healthy subjects. Further studies, however, mostly with small series of patients, did not confirm these results (Cuckle et al, 1990;Spath-Schwalbe et al, 1990;Leblhuber et al, 1993). More recently, observational longitudinal studies failed to demonstrate a predictive role of DHEA levels with respect to development of cognitive decline (Barret-Connor and Edelstein, 1994;Berr et al, 1996;Yaffe et al, 1998), and a randomized trial did not show evidence of benefit from treatment with DHEA in patients with Alzheimer's disease (Wolkowitz et al, 2003).…”

Section: Introductionmentioning

confidence: 83%

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Dehydroepiandrosterone sulfate (DHEA‐S) and Alzheimer's dementia in older subjects

Massaia

Zannella

et al. 2006

Int J Geriat Psychiatry

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 83%

Dehydroepiandrosterone sulfate (DHEA‐S) and Alzheimer's dementia in older subjects

Massaia

Zannella

et al. 2006

Int J Geriat Psychiatry

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“…Whether there is a link between reduced levels of DHEA or DHEAS and AD is still a controversial issue. Most studies have not found differences in DHEAS levels between AD patients and non-demented patients (Legrain et al, 1995;Yanase et al, 1996;Ferrario et al, 1999), whereas two studies have reported decreased levels of DHEAS in AD patients (Leblhuber et al, 1993;Murialdo et al, 2000). No apparent relationship between circulating levels of DHEAS and cognitive performance in the elderly has been found (Barrett-Connor and Edelstein, 1994;Kalmijn et al, 1998;Mazat et al, 2001;Yaffe et al, 1998a).…”

Section: Steroidal Aging In Humansmentioning

confidence: 99%

“…As described above, measures of blood levels of DHEA and DHEAS in AD patients have provided conflicting results (Leblhuber et al, 1993;Legrain et al, 1995;Yanase et al, 1996;Ferrario et al, 1999;Murialdo et al, 2000). A comparative analysis of the concentrations of several neurosteroids in various brain regions between aged AD patients and aged non-demented controls has been recently reported (Weill-Engerer et al, 2002).…”

Section: Analysis Of Neurosteroids In the Brains Of Aged Patients By mentioning

confidence: 99%

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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“…Declining DHEA and DHEA sulfate (DHEAS) levels during aging are associated with pathophysiological effects such as neuronal degeneration (Leblhuber et al, 1993). Recent studies show that DHEA protects rat chromaffin cells and PC12 rat pheochromocytoma cells against serum-deprivation induced apoptosis (Charalampopoulos et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

DHEA-Bodipy—A functional fluorescent DHEA analog for live cell imaging

Lemcke

Hönnscheidt

Waschatko

et al. 2010

Molecular and Cellular Endocrinology

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The androgen dehydroepiandrosterone (DHEA) has been reported to protect neuronal cells against dysfunction and apoptosis. Several signaling pathways involved in these effects have been described but little is known about the intracellular trafficking of DHEA. We describe design, synthesis and characterization of DHEA-Bodipy, a novel fluorescent DHEA analog. DHEA-Bodipy proved to be a functional DHEA derivative: DHEA-Bodipy (i) induced estrogen receptor α-mediated gene activation, (ii) protected PC12 rat pheochromocytoma cells against serum deprivation-induced apoptosis, and (iii) induced stress fibers and focal adhesion contacts in SH-SY5Y human neuroblastoma cells. DHEA-Bodipy bound rapidly and specifically to plasma membranes of living PC12 cells. We analyzed metabolism and trafficking of DHEA-Bodipy in human neuroblastoma cells. DHEA-Bodipy is the first functional fluorescent DHEA derivative suitable for live cell imaging of intracellular DHEA transport and localization.

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Age and sex differences of dehydroepiandrosterone sulfate (DHEAS) and cortisol (CRT) plasma levels in normal controls and Alzheimer's disease (AD)

Cited by 55 publications

References 26 publications

Dehydroepiandrosterone sulfate (DHEA‐S) and Alzheimer's dementia in older subjects

Dehydroepiandrosterone sulfate (DHEA‐S) and Alzheimer's dementia in older subjects

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

DHEA-Bodipy—A functional fluorescent DHEA analog for live cell imaging

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