Affiliations: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314-6399, USA
Correspondence:
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Corresponding author: C.-X. Gong, Head, Brain Metabolism Laboratory, Department of Neurochemistry, USA. Tel.: +1 718 494 5248; Fax: +1 718 494 1080; E-mail: cxgong@ultinet.net
Abstract: Neurofibrillary degeneration characterized by abnormal hyperphosphorylation and aggregation of tau in affected neurons is directly associated with dementia symptoms and plays a pivotal role in the pathogenesis of Alzheimer disease (AD) and related tauopathies. It is well established that brain glucose uptake/metabolism is impaired in AD, but how this impairment contributes to the disease is unknown. We recently found that tau in human brain is also modified by O-GlcNAcylation in addition to phosphorylation and that the former negatively regulates the latter. On the basis of these findings, we propose a novel hypothesis that the impaired glucose uptake/metabolism contributes to AD by facilitating abnormal hyperphosphorylation of tau. Further studies of this mechanism are likely to offer a novel therapeutic target for preventing and treating AD.
