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Growth Hormone and Insulin-Like Growth Factor-I as an Endocrine Axis in Alzheimer's Disease

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment with insidious onset. Neuropathological analysis of AD-affected brains reveals extensive atrophy and an accumulation of neurofibrillary tangles. Taken together, the neurochemical changes in the brain in patients with AD indicate multiple disturbances, and it seems likely that the changes are secondary to more fundamental changes in the brain. The IGF-I is a potent neurotrophic as well as a neuroprotective factor found in the brain, with a wide range of actions in both the central and the peripheral nervous systems. There is a physiological decline of the growth hormone (GH)/insulin-like growth factor- I (IGF-I) axis with ageing, and the possibility that the GH/IGF-I axis is involved in cognitive deficits has been recognized for several years. IGF-I is a critical promoter of brain development and neuronal survival, and plays a role in neuronal rescue during degenerative diseases. The investigations of GH-releasing stimulation tests, and especially of GHRH in AD, are equivocal and in some cases contradictory. The results of several studies addressing this point show varied results: superimposable response of GH to GHRH than response of GH to GHRH in controls; blunted GH to GHRH response in AD patients; higher GH concentrations in the morning; greater increase of GH to GHRH in AD patients than in controls. When an acetylcholinesterase inhibitor, such as rivastigmine, a drug for AD, is acutely administered, the area under the curve of the GH response to GHRH doubles, showing that rivastigmine is a powerful drug in the enhancement of GH release. Consequently, an emerging clinical target for improving the clinical manifestations of AD may be the activation of GH/IGF-I, which rejuvenates the axis, so resulting in an overall physiological benefit.

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Keywords: Acetylcholinesterase inhibitors; Alzheimer's disease; growth hormone; insulin-like growth factor-I; insulin-like growth factor-binding proteins; neurofibrillary tangles

Document Type: Research Article

Publication date: June 1, 2008

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  • This journal is devoted to timely reviews of experimental and clinical studies in the field of endocrine, metabolic, and immune disorders. Specific emphasis is placed on humoral and cellular targets for natural, synthetic, and genetically engineered drugs that enhance or impair endocrine, metabolic, and immune parameters and functions. Topics related to the neuroendocrine-immune axis are given special emphasis in view of the growing interest in stress-related, inflammatory, autoimmune, and degenerative disorders.
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