Estrogen Replacement and Risk of Alzheimer Disease

Smith, Mark A.; Perry, George; Atwood, Craig S.; Bowen, Richard L.

doi:10.1001/jama.289.9.1100-a

Cited by 15 publications

(2 citation statements)

References 21 publications

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“…In AD patients, cognitive impairments and psychological symptoms are associated with an early dysfunction of the HPA [47] and HPG axes [48–51]. However, few studies have investigated neuroendocrine function in APP/PS1 mice or analogous models, although one study reported that plasma CORT levels were increased in 8-month-old male APP/PS1 mice [52].…”

Section: Discussionmentioning

confidence: 99%

LW-AFC, a new formula derived from Liuwei Dihuang decoction, ameliorates behavioral and pathological deterioration via modulating the neuroendocrine-immune system in PrP-hAβPPswe/PS1ΔE9 transgenic mice

Wang¹,

Cheng³

et al. 2016

Alz Res Therapy

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BackgroundAccumulating evidence implicates the neuroendocrine immunomodulation (NIM) network in the physiopathological mechanism of Alzheimer’s disease (AD). Notably, we previously revealed that the NIM network is dysregulated in the PrP-hAβPPswe/PS1ΔE9 (APP/PS1) transgenic mouse model of AD.MethodsAfter treatment with a novel Liuwei Dihuang formula (LW-AFC), mice were cognitively evaluated in behavioral experiments. Neuron loss, amyloid-β (Aβ) deposition, and Aβ level were analyzed using Nissl staining, immunofluorescence, and an AlphaLISA assay, respectively. Multiplex bead analysis, a radioimmunoassay, immunochemiluminometry, and an enzyme-linked immunosorbent assay (ELISA) were used to measure cytokine and hormone levels. Lymphocyte subsets were detected using flow cytometry. Data between two groups were compared using a Student’s t test. Comparison of the data from multiple groups against one group was performed using a one-way analysis of variance (ANOVA) followed by a Dunnett’s post hoc test or a two-way repeated-measures analysis of variance with a Tukey multiple comparisons test.ResultsLW-AFC ameliorated the cognitive impairment observed in APP/PS1 mice, including the impairment of object recognition memory, spatial learning and memory, and active and passive avoidance. In addition, LW-AFC alleviated the neuron loss in the hippocampus, suppressed Aβ deposition in the brain, and reduced the concentration of Aβ1–42 in the hippocampus and plasma of APP/PS1 mice. LW-AFC treatment also significantly decreased the secretion of corticotropin-releasing hormone and gonadotropin-releasing hormone in the hypothalamus, and adrenocorticotropic hormone, luteinizing hormone, and follicle-stimulating hormone in the pituitary. Moreover, LW-AFC increased CD8+CD28+ T cells, and reduced CD4+CD25+Foxp3+ T cells in the spleen lymphocytes, downregulated interleukin (IL)-1β, IL-2, IL-6, IL-23, granulocyte-macrophage colony stimulating factor, and tumor necrosis factor-α and -β, and upregulated IL-4 and granulocyte colony stimulating factor in the plasma of APP/PS1 mice.ConclusionsLW-AFC ameliorated the behavioral and pathological deterioration of APP/PS1 transgenic mice via the restoration of the NIM network to a greater extent than either memantine or donepezil, which supports the use of LW-AFC as a potential agent for AD therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-016-0226-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

LW-AFC, a new formula derived from Liuwei Dihuang decoction, ameliorates behavioral and pathological deterioration via modulating the neuroendocrine-immune system in PrP-hAβPPswe/PS1ΔE9 transgenic mice

Wang¹,

Cheng³

et al. 2016

Alz Res Therapy

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“…A preclinical study suggested that lowering LH levels might be beneficial in AD [28]. Increased LH levels have been found in brain in patients with AD [29,30]. Treatment of C57/Bl6 wild-type mice with leuprolide decreases Aβ levels.…”

Section: Hormonal Therapies: Estrogen and Leuprolidementioning

confidence: 99%

Investigational drugs for the treatment of AD: what can we learn from negative trials?

Jacobson

Sabbagh

2011

Alzheimers Res Ther

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Given the level of interest and activity in the race to find a treatment for Alzheimer's disease, it is expected that a reasonably safe and effective drug will be identified within the next decade. It may be worthwhile to pause periodically during the course of this race to take stock of what we have learned. Over the past few years, a number of trials have been conducted with promising new compounds (including some with novel mechanisms of action) that failed to meet primary endpoints and so were discontinued from clinical development. This article reviews a set of molecules with a range of mechanisms that have been trialed but with negative results. This article also examines the reasons for the negative findings and summarizes some of what we have learned from these experiences.

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Current awareness in geriatric psychiatry

2003

Int J Geriat Psychiatry

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of geriatric psychiatry. Each bibliography is divided into 9 sections: 1 Books, Reviews & Symposia; 2 General; 3 Assessment; 4 Epidemiology; 5 Therapy; 6 Care; 7 Dementia; 8 Depression; 9 Psychology. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted

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Estrogen Replacement and Risk of Alzheimer Disease

Cited by 15 publications

References 21 publications

LW-AFC, a new formula derived from Liuwei Dihuang decoction, ameliorates behavioral and pathological deterioration via modulating the neuroendocrine-immune system in PrP-hAβPPswe/PS1ΔE9 transgenic mice

LW-AFC, a new formula derived from Liuwei Dihuang decoction, ameliorates behavioral and pathological deterioration via modulating the neuroendocrine-immune system in PrP-hAβPPswe/PS1ΔE9 transgenic mice

Investigational drugs for the treatment of AD: what can we learn from negative trials?

Current awareness in geriatric psychiatry

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