title: Increased cerebrospinal fluid levels of double-stranded RNA-dependant protein kinase in Alzheimer's disease.
abstract: 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.affiliation: Memory Clinical Center, Lariboisiere Fernand Widal Saint Louis Hospital, Assistance Publique -Hôpitaux de Paris, University of Paris Diderot, France.
authors.forename: François
authors.initials: F
authors.lastname: Mouton-Liger
authors.forename: Claire
authors.initials: C
authors.lastname: Paquet
authors.forename: Julien
authors.initials: J
authors.lastname: Dumurgier
authors.forename: Pauline
authors.initials: P
authors.lastname: Lapalus
authors.forename: Françoise
authors.initials: F
authors.lastname: Gray
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Laplanche
authors.forename: Jacques
authors.initials: J
authors.lastname: Hugon
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000201:enzymology* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000201:enzymology* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000201:enzymology / Q000378:metabolism; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D012372:ROC Curve; D012680:Sensitivity and Specificity; D019892:eIF-2 Kinase / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D019892:eIF-2 Kinase