An Association with Great Implications: Vascular Pathology and Alzheimer Disease

Alzheimer Disease and Associated Disorders (Impact Factor: 2.44). 01/2006; 20(1):73-5. DOI: 10.1097/01.wad.0000201855.39246.2d
Source: PubMed
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    ABSTRACT: Summary form only given. It is pointed out that, whether one is developing a simple or a complex product, the product design and development cycle can be accelerated by adopting an approach that stresses planning, close teamwork, superior communication, realistic evaluation procedures, and full use of available tools and resources. Planning begins with a clear definition of the product rationale, a description of the product, and an assessment of cost, problem areas, and resources. The plan also includes realistic milestones and performance measures. Experienced staff should prepare or oversee the product development plan. Team work and communication are key elements of the project's success along with evaluation procedures that allow for identifying early problem areas and prescribing conditions for continuing, redirecting, or terminating projects. Highly developed communication networks and a responsive decision-making process are cornerstones of successful product development projects. Finally, the planning process identifies the need for resources such as new technology to substitute for existing ones or to develop breakthrough products, a new support environment, and outside expertise
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    ABSTRACT: Alzheimers disease (AD) can be viewed as a vicious cycle in which excess production and deposition of amyloid beta (Abeta) peptides promote microglial activation, and the resultant production of inflammatory mediators further boosts Abeta production while inducing death and dysfunction of neurons. Abeta production is mediated by beta- and gamma-secretase activities; it is prevented by alpha-secretase activity, and insulin-degrading enzyme (IDE) catabolizes Abeta. High cellular cholesterol content increases Abeta synthesis by boosting beta-secretase activity; inhibition of cholesterol syntheses and/or stimulation of cholesterol export thus diminishes Abeta production. PPARgamma activity decreases Abeta production by promoting harmless catabolism of amyloid precursor protein while blocking the up-regulatory impact of cytokines on beta-secretase expression. Nitric oxide produced by the healthy cerebral microvasculature can suppress Abeta production by boosting expression of alpha-secretase while suppressing that of beta-secretase; conversely, cerebral ischemia provokes increased APP expression. Good insulin sensitivity and efficient brain insulin function protect by inhibiting gamma-secretase activity and increasing expression of IDE. The DHA provided by fish oil diminishes cerebral Abeta deposition in rodent AD models, for unclear reasons. Various measures which oppose microglial activation can inhibit up-regulation of beta-secretase and gamma-secretase by oxidants and cytokines, respectively. These considerations suggest that a number of nutraceutical or lifestyle measures may have potential for preventing or slowing AD: policosanol; 9-cis-beta-carotene; isomerized hops extract; DHA; measures which promote efficient endothelial NO generation, such as low-salt/potassium-rich diets, exercise training, high-dose folate, and flavanol-rich cocoa; chromium picolinate and cinnamon extract as aids for insulin sensitivity; and various agents which can oppose microglial activation, including vitamin D, genistein, and sesamin. The impact of these measures on Abeta production in rodent models of AD should be evaluated, with the intent of defining practical strategies for AD prevention.
    Medical Hypotheses 02/2006; 67(4):682-97. DOI:10.1016/j.mehy.2006.04.067 · 1.07 Impact Factor
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