Document Detail


Therapeutic targets of brain insulin resistance in sporadic Alzheimer's disease.
MedLine Citation:
PMID:  22201977     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Growing evidence supports roles for brain insulin and insulin-like growth factor (IGF) resistance and metabolic dysfunction in the pathogenesis of Alzheimer's disease (AD). Whether the underlying problem stems from a primary disorder of central nervous system (CNS) neurons and glia, or secondary effects of systemic diseases such as obesity, Type 2 diabetes, or metabolic syndrome, the end-results include impaired glucose utilization, mitochondrial dysfunction, increased oxidative stress, neuroinflammation, and the propagation of cascades that result in the accumulation of neurotoxic misfolded, aggregated, and ubiquitinated fibrillar proteins. This article reviews the roles of impaired insulin and IGF signaling to AD-associated neuronal loss, synaptic disconnection, tau hyperphosphorylation, amyloid-beta accumulation, and impaired energy metabolism, and discusses therapeutic strategies and lifestyle approaches that could be used to prevent, delay the onset, or reduce the severity of AD. Finally, it is critical to recognize that AD is heterogeneous and has a clinical course that fully develops over a period of several decades. Therefore, early and multi-modal preventive and treatment approaches should be regarded as essential.
Authors:
Suzanne M de la Monte
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Publication Detail:
Type:  Journal Article     Date:  2012-01-01
Journal Detail:
Title:  Frontiers in bioscience (Elite edition)     Volume:  4     ISSN:  1945-0508     ISO Abbreviation:  Front Biosci (Elite Ed)     Publication Date:  2012  
Date Detail:
Created Date:  2011-12-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101485240     Medline TA:  Front Biosci (Elite Ed)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1582-605     Citation Subset:  IM    
Affiliation:
Departments of Neurology, Neurosurgery, and Neuropathology, Rhode Island Hospital and the Alpert Medical School of Brown University, Providence, RI.
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