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Increased Cerebrospinal Fluid Levels of Double-Stranded RNA-Dependant Protein Kinase in Alzheimer's Disease.
MedLine Citation:
PMID:  22281122     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: The pathological hallmarks of Alzheimer's disease (AD) include accumulation of amyloid-β (Aß) peptide forming extracellular senile plaques, neurofibrillary tangles made of hyperphosphorylated tau protein with neuronal loss. Aβ peptide (1-42), total tau (T-tau), and phosphorylated tau at threonine 181 (p181tau) levels in the cerebrospinal fluid (CSF) are now validated biomarkers. The proapoptotic kinase R (PKR), is activated by Aβ accumulates in degenerating neurons in AD brains and controls protein synthesis and indirectly tau phosphorylation. METHODS: In a prospective cohort study, the CSF of 91 patients were studied (AD: 45; amnestic mild cognitive impairment: 11; neurological disease control subjects [NDC]: 35). The levels of total PKR (T-PKR), phosphorylated PKR (pPKR), Aß 1-42, T-tau, and p181tau were assessed by immunoblotting or enzyme-linked immunosorbent assay methods. Receivers operating characteristic curves were used to examine the discriminatory power of T-PKR, pPKR, and pPKR/T-PKR ratio between AD and NDC patients. RESULTS: Total PKR and pPKR concentrations were elevated in AD and amnestic mild cognitive impairment subjects. We have determined a pPKR value (optical density units) that could discriminate AD patients from control subjects with a sensitivity of 91.1% and a specificity of 94.3%. Among AD patients, T-PKR and pPKR levels correlate with CSF p181tau levels. Some AD patients with normal CSF Aß, T-tau, or p181tau levels had abnormal T-PKR and pPKR levels. CONCLUSIONS: The evaluation of CSF T-PKR and pPKR can discriminate between AD patients and NDC and could help to improve the biochemical diagnosis of AD.
Authors:
François Mouton-Liger; Claire Paquet; Julien Dumurgier; Pauline Lapalus; Françoise Gray; Jean-Louis Laplanche; Jacques Hugon;
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-24
Journal Detail:
Title:  Biological psychiatry     Volume:  -     ISSN:  1873-2402     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0213264     Medline TA:  Biol Psychiatry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Affiliation:
Memory Clinical Center, Lariboisiere Fernand Widal Saint Louis Hospital, Assistance Publique -Hôpitaux de Paris, University of Paris Diderot, Paris, France; Institut du Fer à Moulin Inserm UMRS 839, Lariboisiere Fernand Widal Saint Louis Hospital, Assistance Publique -Hôpitaux de Paris, University of Paris Diderot, Paris, France; Department of Histology, Lariboisiere Fernand Widal Saint Louis Hospital, Assistance Publique -Hôpitaux de Paris, University of Paris Diderot, Paris, France.
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