Journal of Alzheimer's disease : JAD
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β-Asarone, an active component of the Acori graminei rhizome that has been used as traditional Chinese herb, has been reported to be capable of inhibiting neuronal apoptosis. However, the signaling mechanism underlying the inhibitory effect of β-asarone has remained elusive. This study was aimed to investigate whether the CaMKII signaling pathway is involved in the β-asarone mediated neuroprotection. ⋯ A significant increase in CaMKII/CREB/Bcl-2 expression was observed in the cortex of the AβPP/PS1 mice treated with β-asarone. In summary, our observations demonstrated that β-asarone can inhibit neuronal apoptosis via the CaMKII/CREB/Bcl-2 signaling pathway in in vitro models and in AβPP/PS1 mice. Therefore, β-asarone can be used as a potential therapeutic agent in the long-term treatment of Alzheimer's disease.
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Biomarkers, both biological and imaging, are indicators of specific changes that characterize Alzheimer's disease (AD) progression in vivo. Knowing the precise relationship between biomarkers and disease severity would allow for accurate disease staging and possible forecasting of decline. Jack et al. suggested as an initial hypothesis that this relationship be sigmoidal; the objective of this article is to determine, using large-scale population data from ADNI, the precise shape of this association. ⋯ Analysis of this cross-sectional dataset showed that a local quadratic regression model was 42% more likely than a sigmoid to be the best model for Aβ42. This ratio augments to 22% and 73% for Penalized B-Spline in the case of p-tau and t-tau, respectively; to 3500% for the linear model for FDG-PET; and to 6700% for the Penalized B-Spline for hippocampal volumes. Preliminary, cross-sectional evidence therefore indicates that the shape of the association with disease severity is non-linear and differs between biomarkers.
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Alzheimer's disease (AD) is characterized by progressive cognitive deficits, accumulation of amyloid-β (Aβ) and intracellular neurofibrillary tangles, and neuronal death. Additionally, mitochondrial dysfunction and free radical damage are hallmarks of AD brain. Here we set out to define the role of oxidative stress in AD pathogenesis and progression by chronically treating 3xTg-AD mice with the superoxide dismutase (SOD)/catalase mimetic, EUK-207. ⋯ The effects of a 3-month treatment after pathology onset at 9 months on cognitive performance, brain oxidative stress, Aβ, and tau pathology were also evaluated. EUK-207-treated 3xTg-AD mice did not display any deficit in fear conditioning and were protected against increases in brain levels of oxidized nucleic acids and lipid peroxidation; they also had reduced Aβ, tau, and hyperphosphorylated tau accumulation in amygdala and hippocampus. Our results confirm a critical role for oxidative stress in AD pathogenesis and progression and suggest the potential usefulness of EUK-207 in AD treatment.
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Cumulative evidence of gray matter abnormalities in semantic dementia (SD) has been reported using voxel-based morphometry (VBM). However, these studies have not been reviewed quantitatively. To estimate gray matter changes in SD quantitatively, we systematically searched whole-brain VBM studies comparing SD patients with healthy controls in the PubMed, ISI Web of Science, and EMABSE databases from January 1990 to August 2011. ⋯ Gray matter volume reductions were found in bilateral fusiform and inferior temporal gyri, extending to the medial portion of the temporal lobes (including amygdala and parahippocampal gyri), left temporal pole, middle temporal gyrus, and caudate. No significant increase in gray matter volume was found. Our findings provide strong evidence of atrophy in bilateral temporal lobes with predominate impairment on the left side, parahippocampal gyrus/amygdala, and left caudate, representing the pathophysiology of SD.
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Level of adiposity is linked to manifest dementia and Alzheimer's disease in epidemiological studies. Overweight and obesity in mid- and late-life may increase risk for dementia, whereas decline in body weight or body mass index and underweight in years preceding and at the time of a dementia diagnosis may also relate to dementia. ⋯ These mechanisms relate to: a) adipose tissue location and cell types, b) body composition, c) endocrine adipose, and d) the interplay among adipose, brain structure and function, and genes. This review will illustrate that adipose tissue is a quintessential, multifunctional tissue of the human body.