Alzheimer's research & therapy
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Alzheimers Res Ther · Jan 2013
Neuroprotective effects of D-Ala(2)GIP on Alzheimer's disease biomarkers in an APP/PS1 mouse model.
Type 2 diabetes mellitus has been identified as a risk factor for Alzheimer's disease (AD). An impairment of insulin signaling as well as a desensitization of its receptor has been found in AD brains. Glucose-dependent insulinotropic polypeptide (GIP) normalises insulin signaling by facilitating insulin release. GIP directly modulates neurotransmitter release, LTP formation, and protects synapses from the detrimental effects of beta-amyloid fragments on LTP formation, and cell proliferation of progenitor cells in the dentate gyrus. Here we investigate the potential therapeutic property of the new long lasting incretin hormone analogue D-Ala(2)GIP on key symptoms found in a mouse model of Alzheimer' disease (APPswe/PS1detaE9). ⋯ The results demonstrate that D-Ala(2)GIP has neuroprotective properties on key hallmarks found in AD. This finding shows that novel GIP analogues have the potential as a novel therapeutic for AD.
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Alzheimers Res Ther · Jan 2013
ReviewEpidemiology of neurodegeneration in American-style professional football players.
The purpose of this article is to review the history of head injuries in relation to American-style football play, summarize recent research that has linked football head injuries to neurodegeneration, and provide a discussion of the next steps for refining the examination of neurodegeneration in football players. For most of the history of football, the focus of media reports and scientific studies on football-related head injuries was on the acute or short-term effects of serious, traumatic head injuries. Beginning about 10 years ago, a growing concern developed among neurologists and researchers about the long-term effects that playing professional football has on the neurologic health of the players. ⋯ Significant progress has been made in the last few years on detecting and defining the pathology of neurodegenerative diseases. However, less progress has been made on other factors related to the progression of those diseases in football players. This review identifies three areas for further research: (a) quantification of exposure - a consensus is needed on the use of clinically practical measurements of blows to the head among football players; (b) genetic susceptibility factors - a more rigorous set of unbiased epidemiological and clinical studies is needed before any causal relationships can be drawn between suspected genetic factors, head injury, and neurodegeneration; and (c) earlier detection and prevention of neurodegenerative diseases.
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The oligomer cascade hypothesis, which states that oligomers are the initiating pathologic agents in Alzheimer's disease, has all but supplanted the amyloid cascade hypothesis, which suggested that fibers were the key etiologic agents in Alzheimer's disease. We review here the results of in vivo, in vitro and in silico studies of amyloid β-protein oligomers, and discuss important caveats that should be considered in the evaluation of these results. ⋯ These multiple orthogonal approaches have revealed much about the molecular and cell biology of amyloid β-protein. However, as informative as these approaches have been, the amyloid β-protein oligomer system remains enigmatic.
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Alzheimers Res Ther · Jan 2013
Memantine in patients with Alzheimer's disease receiving donepezil: new analyses of efficacy and safety for combination therapy.
Memantine and cholinesterase inhibitors potentially offer additional benefits in Alzheimer's disease (AD) when used together. This study assessed the efficacy and safety of combination treatment with memantine added to stable donepezil in patients with moderate to severe AD, and in a subset with moderate AD. ⋯ These results support and extend previous evidence that combination treatment with memantine added to stable donepezil in patients with moderate AD, and in those with moderate to severe AD, is associated with significant benefits in reducing 24-week decline in cognition, function and global status. Combination treatment produces substantially reduced rates of marked clinical worsening, has good safety and tolerability, and generates effect sizes that are both statistically significant and clinically meaningful.
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Alzheimers Res Ther · Jan 2013
Should interventions to treat or prevent Alzheimer's disease be tested in a population or as targeted treatment of highly selected study participants?
Symptomatic treatments for Alzheimer's disease should retain a place in the advanced stages of disease since their actions on these symptoms, even if not modifying the course of disease, are critical for improving patients' comfort and reducing the burden felt by caregivers, especially those facing behavioral disorders. In mild or prodromal stages, the opportunity to act on specific pathophysiological targets should be considered. These targeted and tailored therapies have the greatest chance to be active in the early stages of disease, in the context of heterogeneous pathological mechanisms to be specified by reliable and accessible biomarkers. Finally, interventional approaches in large populations seem particularly appropriate for prevention strategies.