Increased cerebrospinal fluid levels of double-stranded RNA-dependant protein kinase in Alzheimer's disease

Biol Psychiatry. 2012 May 1;71(9):829-35. doi: 10.1016/j.biopsych.2011.11.031. Epub 2012 Jan 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / enzymology*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Case-Control Studies
  • Cell Line, Tumor
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / enzymology*
  • Cognitive Dysfunction / metabolism
  • Disease Progression
  • Female
  • Hippocampus / enzymology
  • Hippocampus / metabolism
  • Humans
  • Male
  • Middle Aged
  • Nervous System Diseases / cerebrospinal fluid
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / enzymology
  • Nervous System Diseases / metabolism
  • Peptide Fragments / cerebrospinal fluid
  • Phosphorylation
  • ROC Curve
  • Sensitivity and Specificity
  • eIF-2 Kinase / cerebrospinal fluid*
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins
  • eIF-2 Kinase