Correlation of Alzheimer-like Tau Hyperphosphorylation and fMRI Bold Intensity

Authors: Xiao-Chuan W.; Zheng-Hui H.; Zheng-Yu F.; Yue F.; Yun-Huang Y.; Qun W.; Xiao-Wei T.; Yi-Gen W.; Jian-Zhi W.

Source: Current Alzheimer Research, Volume 1, Number 2, May 2004 , pp. 143-148(6)

Publisher: Bentham Science Publishers

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Abstract:

To explore the correlation between cerebral functional alterations revealed by functional magnetic resonance imaging (fMRI) and Alzheimer disease- (AD)-like tau hyperphosphorylation, we injected bilaterally 2 mgr

l each of 20 mM isoproterenol (IP), a PKA activator, or of saline as a vehicle control into the hippocampus of rats. FMRI was employed to measure the intensity of BOLD signal, one of the cerebral functional markers reflecting the changes of cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF), in hippocampus and cortex 24 h after the operation. Immunohistochemical staining of hippocampus and cortex was carried out using phosphorylation-dependent tau antibodies. The results showed (1) that BOLD intensity in hippocampus and cortex of IP-injected rats was obviously lower than that of sham-operated group, indicating a decrease in CMRO2 and CBF of the particular brain regions in IPtreated rats; (2) that tau was hyperphosphorylated at Ser-262 / Ser-356 (12e8), Ser-396 / Ser-404 (PHF-1) sites in CA1 CA2 CA3 CA4 and dentate gyrus regions of hippocampal formation and cortex area in IP group, but not in sham rats; (3) that a negative correlation between tau hyperphosphorylation and BOLD intensity in hippocampus and cortex area of IP rats was observed. The data suggested that hippocampal and cortical tau hyperphosphorylation was intimately related to BOLD intensity of the same areas. To our knowledge, this is the first report exploring the relationship between fMRI BOLD signal and AD-like tau hyperphosphorylation.

Keywords: alzheimers disease; tau; hyperphosphorylation; Isoproterenol; fmri; bold signal; cmro2; cbf

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1567205043332216

Affiliations: 1: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, WuHan, 430030, P.R. China

Publication date: 2004-05-01

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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.

Correlation of Alzheimer-like Tau Hyperphosphorylation and fMRI Bold Intensity

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