Insulin Resistance and Alzheimer's Disease Pathogenesis: Potential Mechanisms and Implications for Treatment
Insulin modulates cognition and other aspects of normal brain function. Insulin resistance is characterized by chronic peripheral insulin elevations, and it is accompanied by reduced brain insulin levels and insulin activity. Obesity, type 2 diabetes mellitus and hypertension are strongly associated with insulin resistance. In addition, insulin resistance increases the risk of age-related memory impairment and Alzheimer's disease. Possible mechanisms through which these risks are increased include the effects of peripheral hyperinsulinemia on memory, CNS inflammation, and regulation of the β-amyloid peptide. We have shown that raising plasma insulin in humans to levels that characterize patients with insulin resistance increases the levels of Aβ and inflammatory agents in brain. These convergent effects may impair memory and induce AD pathology. Therapeutic strategies focused on preventing or correcting insulin abnormalities may thus benefit a subset of adults with age-related memory impairment and AD.
Document Type: Research Article
Affiliations: GRECC S-182, VAPSHCS,1660 S. Columbian Way, Seattle, WA, 98108, USA.
Publication date: April 1, 2007
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- Current Alzheimer Research publishes peer-reviewed frontier review and research articles on all areas of Alzheimer's disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer's disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer's disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer's disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer's disease. Current Alzheimer Research provides a comprehensive 'bird's-eye view' of the current state of Alzheimer's research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.
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