Growth Factors Decrease in Subjects With Mild to Moderate Alzheimer's Disease (Ad): Potential Correction With Dehydroepiandrosterone-Sulphate (Dheas)

Luppi, Chiara; Fioravanti, Marisa; Bertolini, Boris; Inguscio, M.; Grugnetti, Anna Maria; Guerriero, F.; Rovelli, C.; Cantoni, Francesca; Guagnano, P.; Marazzi, E; Rolfo, E.; Ghianda, Diego; Levante, D.; Guerrini, Chiara; R, Bonacasa; Solerte, Sebastiano Bruno

doi:10.1016/j.archger.2009.09.027

Cited by 32 publications

(19 citation statements)

References 23 publications

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“…As the brain ages, among other alterations that may adversely affect neuronal survival, neurotrophic factor synthesis/signalling decreases (Bishop et al 2010; Katoh-Semba et al 1998; Sonntag et al 1999; Tapia-Arancibia et al 2008; Luppi et al 2009) and oxidative stress and free radicals accumulate (Hanawalt 2008). Importantly for age-related Purkinje cell death, sex steroids regulate both these processes.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly for age-related Purkinje cell death, sex steroids regulate both these processes. First, sex steroids promote the expression and signalling of brain-derived neurotrophic factor (BDNF; Begliuomini et al 2007; Kaur et al 2007) and insulin-like growth factor-1 (IGF-1; Garcia-Segura et al 2006; Alonso et al 2008; Luppi et al 2009), both of which are survival factors for Purkinje cells (Larkfors et al 1996; Lindholm et al 1997; Fukudome et al 2003). Indeed the neuroprotective action of oestrogen and progesterone are mediated through BDNF and IGF-1 receptor signalling and their downstream pathways through MAP kinase and phosphatidylinositol-3 kinase (Garcia-Segura et al 2006; Kaur et al 2007; Alonso et al 2008).…”

Section: Discussionmentioning

confidence: 99%

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Age-related Purkinje cell death is steroid dependent: RORα haplo-insufficiency impairs plasma and cerebellar steroids and Purkinje cell survival

Janmaat

Akwa

Doulazmi

et al. 2011

AGE

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A major problem of ageing is progressive impairment of neuronal function and ultimately cell death. Since sex steroids are neuroprotective, their decrease with age may underlie age-related neuronal degeneration. To test this, we examined Purkinje cell numbers, plasma sex steroids and cerebellar neurosteroid concentrations during normal ageing (wild-type mice, WT), in our model of precocious ageing (Rora+/sg, heterozygous staggerer mice in which expression of the neuroprotective factor RORα is disrupted) and after long-term hormone insufficiency (WT post-gonadectomy). During normal ageing (WT), circulating sex steroids declined prior to or in parallel with Purkinje cell loss, which began at 18 months of age. Although Purkinje cell death was advanced in WT long-term steroid deficiency, this premature neuronal loss did not begin until 9 months, indicating that vulnerability to sex steroid deficiency is a phenomenon of ageing Purkinje neurons. In precocious ageing (Rora+/sg), circulating sex steroids decreased prematurely, in conjunction with marked Purkinje cell death from 9 months. Although Rora+/sg Purkinje cells are vulnerable through their RORα haplo-insufficiency, it is only as they age (after 9 months) that sex steroid failure becomes critical. Finally, cerebellar neurosteroids did not decrease with age in either genotype or gender; but were profoundly reduced by 3 months in male Rora+/sg cerebella, which may contribute to the fragility of their Purkinje neurons. These data suggest that ageing Purkinje cells are maintained by circulating sex steroids, rather than local neurosteroids, and that in Rora+/sg their age-related death is advanced by premature sex steroid loss induced by RORα haplo-insufficiency.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Age-related Purkinje cell death is steroid dependent: RORα haplo-insufficiency impairs plasma and cerebellar steroids and Purkinje cell survival

Janmaat

Akwa

Doulazmi

et al. 2011

AGE

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“…Similarly, AD patients have been demonstrated to show a reduction in the plasma levels of the active (25 kDa) and inactive (50 kDa) forms of TGF-β1 (Mocali et al 2004;Juraskova et al 2010) and a reduced secretion of TGF-β1 from circulating peripheral blood mononuclear cells (Luppi et al 2009). Interestingly, Tesseur et al (2009) have found that TGF-β1 associates with plasma lipoproteins, and most importantly, that bioactive TGF-β1 is enriched in lipoproteins containing apolipoprotein E3 (apoE3) but occurs at a lower concentration in lipoproteins containing apoE4, an established genetic risk factor for of late-onset AD (Corder et al 1993).…”

Section: The Pathogenesis Of Alzheimer's Diseasementioning

confidence: 97%

Dysfunction of TGF-β1 signaling in Alzheimer’s disease: perspectives for neuroprotection

et al. 2011

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Alzheimer's disease (AD) is a neurodegenerative disorder that affects about 35 million people worldwide. Current drugs for AD only treat the symptoms and do not interfere with the underlying pathogenic mechanisms of the disease. AD is characterized by the presence of β-amyloid (Aβ) plaques, neurofibrillary tangles, and neuronal loss. Identification of the molecular determinants underlying Aβ-induced neurodegeneration is an essential step for the development of disease-modifying drugs. Recently, an impairment of the transforming growth factor-β1 (TGF-β1) signaling pathway has been demonstrated to be specific to the AD brain and, particularly, to the early phase of the disease. TGF-β1 is a neurotrophic factor responsible for the initiation and maintenance of neuronal differentiation and synaptic plasticity. The deficiency of TGF-β1 signaling is associated with Aβ pathology and neurofibrillary tangle formation in AD animal models. Reduced TGF-β1 signaling seems to contribute both to microglial activation and to ectopic cell-cycle re-activation in neurons, two events that contribute to neurodegeneration in the AD brain. The neuroprotective features of TGF-β1 indicate the advantage of rescuing TGF-β1 signaling as a means to slow down the neurodegenerative process in AD.

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“…21,22 While acute stress typically leads to increases in DHEA-S, prolonged exposure to stressors attenuates DHEA-S levels, thereby reducing its health protective effects. 8,20 DHEA-S levels also decrease with age. 10 Thus, older people experiencing chronic high levels of stressor exposure may be particularly vulnerable to depletion of DHEA-S.…”

mentioning

confidence: 89%

“…19 Higher levels of DHEA-S may have possible neuroprotective effects in aging and Alzheimer’s disease. 20 In turn, low levels of DHEA-S among older people have been linked to cancer, insulin resistance, cardiovascular disease, and immune system deficiencies. 21,22 While acute stress typically leads to increases in DHEA-S, prolonged exposure to stressors attenuates DHEA-S levels, thereby reducing its health protective effects.…”

mentioning

confidence: 99%

Daily Stressors and Adult Day Service Use by Family Caregivers: Effects on Depressive Symptoms, Positive Mood, and Dehydroepiandrosterone-Sulfate

Zarit¹,

Whetzel²,

Kim³

et al. 2014

The American Journal of Geriatric Psychiatry

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Objectives This study examines effects of daily use of adult day services (ADS) programs by caregivers of individuals with dementia (IWD) on a salivary biomarker of stress reactivity, dehydroepiandrosterone-sulfate (DHEA-S), and whether these effects on DHEA-S are associated with daily variability in positive mood and depressive symptoms. Design We used a daily diary design of 8 consecutive days with alternation of intervention (ADS) and non-intervention days to evaluate within- and between-person effects of the intervention. Setting Caregivers were interviewed daily by telephone at home. Participants 151 family caregivers of IWD who were using ADS. Measurements Saliva samples were collected from caregivers 5 times a day for 8 consecutive days and were assayed for DHEA-S. Daily telephone interviews assessed daily stressors and mood. Results DHEA-S levels were significantly higher on days following ADS use. Daily DHEA-S levels covaried significantly with daily positive mood, but not depressive symptoms. Conclusions These results demonstrate an association of ADS use by family caregivers and higher DHEA-S levels on the next day. Prior research has found that higher DHEA-S levels are protective against the physiological damaging effects of stressor exposure and may reduce risks of illness. Regular use of ADS may help reduce depletion of DHEA-S and allow the body to mount a protective and restorative response to the physiological demands of caregiving. To our knowledge, this is the first study to examine DHEA-S levels across the day in connection with an intervention that affected daily exposure to stressors.

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Growth Factors Decrease in Subjects With Mild to Moderate Alzheimer's Disease (Ad): Potential Correction With Dehydroepiandrosterone-Sulphate (Dheas)

Cited by 32 publications

References 23 publications

Age-related Purkinje cell death is steroid dependent: RORα haplo-insufficiency impairs plasma and cerebellar steroids and Purkinje cell survival

Age-related Purkinje cell death is steroid dependent: RORα haplo-insufficiency impairs plasma and cerebellar steroids and Purkinje cell survival

Dysfunction of TGF-β1 signaling in Alzheimer’s disease: perspectives for neuroprotection

Daily Stressors and Adult Day Service Use by Family Caregivers: Effects on Depressive Symptoms, Positive Mood, and Dehydroepiandrosterone-Sulfate

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