| Increased Cerebrospinal Fluid Levels of Double-Stranded RNA-Dependant Protein Kinase in Alzheimer's Disease. | |
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MedLine Citation:
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PMID: 22281122 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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François Mouton-Liger; Claire Paquet; Julien Dumurgier; Pauline Lapalus; Françoise Gray; Jean-Louis Laplanche; Jacques Hugon; |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-24 |
Journal Detail:
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Title: Biological psychiatry Volume: - ISSN: 1873-2402 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0213264 Medline TA: Biol Psychiatry Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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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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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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