Relationship between Alzheimer's disease clinical stage and Gq/11 in subcellular fractions of frontal cortex

Alzheimer's disease (AD) is associated with impaired coupling of cell surface muscarinic cholinergic receptors to G proteins of the Gq/11 class in brain. This alteration may contribute to progression of cognitive impairment during the course of the disease. We hypothesized that increasing sever...

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Bibliographic Details
Published in:Journal of Neural Transmission 2005-08, Vol.112 (8), p.1049-1056
Main Authors: Kelly, J F, Storie, K, Skamra, C, Bienias, J, Beck, T, Bennett, D A
Format: Article
Language:English
Subjects:
Age Factors
Aged
Aged, 80 and over
Alzheimer Disease - metabolism
Alzheimer Disease - physiopathology
Alzheimer Disease - psychology
Cognition Disorders - diagnosis
Cognition Disorders - etiology
Cognition Disorders - metabolism
Cytoplasm - metabolism
Disease Progression
Educational Status
Female
Frontal Lobe - metabolism
Frontal Lobe - pathology
Frontal Lobe - physiopathology
GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism
Humans
Male
Membrane Microdomains - metabolism
Microsomes - metabolism
Neuropsychological Tests
Receptors, Muscarinic - metabolism
Regression Analysis
Sex Factors
Subcellular Fractions
Synaptic Membranes - metabolism
Synaptic Transmission - physiology
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Summary:Alzheimer's disease (AD) is associated with impaired coupling of cell surface muscarinic cholinergic receptors to G proteins of the Gq/11 class in brain. This alteration may contribute to progression of cognitive impairment during the course of the disease. We hypothesized that increasing severity of cognitive impairment would be related to decreased levels of Gq/11 detected in key subcellular fractions made from postmortem brain tissue. In this study, we used Western blotting to determine the quantity of Gq/11alpha in P2, synaptic plasma membrane, cytoplasm, microsomal membrane, and lipid raft fractions prepared from superior frontal cortex gray matter of 25 patients with clinical AD confirmed by post-mortem examination. Multiple linear regression analysis that adjusted for age, sex, and education showed a linear relationship between frontal cortex synaptic plasma membrane Gq/11alpha levels and severity of cognitive impairment determined by Mini Mental State score measured proximate to death.
ISSN:0300-9564
1435-1463
DOI:10.1007/s00702-004-0243-7