Articles: amyloid-metabolism.
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Archives of neurology · Feb 2011
Mass spectrometric-based proteomic analysis of amyloid neuropathy type in nerve tissue.
To determine the specific type of amyloid from nerve biopsies using laser microdissection (LMD) and mass spectrometric (MS)-based proteomic analysis. ⋯ Proteomic analysis of nerve tissue using LMD/MS distinguishes specific types of amyloid independent of clinical information. This new proteomic approach will enhance both diagnostic and research efforts in amyloidosis and other neurologic diseases.
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Evidence of reduced blood-brain barrier (BBB) integrity preceding other Alzheimer's disease (AD) pathology provides a strong link between cerebrovascular angiopathy and AD. However, the "Vascular hypothesis", holds that BBB leakiness in AD is likely due to hypoxia and neuroinflammation leading to vascular deterioration and apoptosis. We propose an alternative hypothesis: amyloidogenesis promotes extensive neoangiogenesis leading to increased vascular permeability and subsequent hypervascularization in AD. ⋯ Hypervascularity in human patients was corroborated in a comparison of postmortem brain tissues from AD and controls. Our results demonstrate that amylodogenesis mediates BBB disruption and leakiness through promoting neoangiogenesis and hypervascularity, resulting in the redistribution of TJs that maintain the barrier and thus, provides a new paradigm for integrating vascular remodeling with the pathophysiology observed in AD. Thus the extensive angiogenesis identified in AD brain, exhibits parallels to the neovascularity evident in the pathophysiology of other diseases such as age-related macular degeneration.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Aug 2010
Noradrenergic neurons of the area postrema mediate amylin's hypophagic action.
Circulating amylin inhibits food intake via activation of the area postrema (AP). The aim of this study was to identify the neurochemical phenotype of the neurons mediating amylin's hypophagic action by immunohistochemical and feeding studies in rats. Expression of c-Fos protein was used as a marker for neuronal activation and dopamine-beta-hydroxylase (DBH), the enzyme-catalyzing noradrenaline synthesis, as a marker for noradrenergic neurons. ⋯ The AP and nucleus of the solitary tract (NTS) were stained for DBH to assess noradrenaline lesion success and for c-Fos expression to evaluate amylin-induced neuronal activation. In contrast to sham-lesioned animals, noradrenaline-lesioned rats did not show a significant increase in amylin-induced c-Fos expression in the AP and NTS. We conclude that the noradrenergic neurons in the AP mediate at least part of amylin's hypophagic effect.
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Clinical Trial
In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F 18).
An (18)F-labeled PET amyloid-beta (Abeta) imaging agent could facilitate the clinical evaluation of late-life cognitive impairment by providing an objective measure for Alzheimer disease (AD) pathology. Here we present the results of a clinical trial with (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine ((18)F-AV-45 or florbetapir [corrected] F 18). ⋯ (18)F-AV-45 was well tolerated, and PET showed significant discrimination between AD patients and HCs, using either a parametric reference region method (DVR) or a simplified SUVR calculated from 10 min of scanning 50-60 min after (18)F-AV-45 administration.
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Ten million baby boomers in the United States will get Alzheimer's disease. Optometrists can benefit from understanding the impact the Alzheimer's disease process has on the visual system. This can result in more effective management of the condition and in more effective communication with members of the Alzheimer's disease multidisciplinary team. ⋯ The effects of Alzheimer's disease are devastating. Optometrists, as primary care clinicians, can make critical contributions in the diagnosis, treatment, and management of this neurodegenerative disease.