Cerebrospinal fluid PKR level predicts cognitive decline in Alzheimer's disease

PLoS One. 2013;8(1):e53587. doi: 10.1371/journal.pone.0053587. Epub 2013 Jan 8.

Abstract

The cerebrospinal fluid (CSF) levels of the proapoptotic kinase R (PKR) and its phosphorylated PKR (pPKR) are increased in Alzheimer's disease (AD), but whether CSF PKR concentrations are associated with cognitive decline in AD patients remain unknown. In this study, 41 consecutive patients with AD and 11 patients with amnestic mild cognitive impairment (aMCI) from our Memory Clinic were included. A lumbar puncture was performed during the following month of the clinical diagnosis and Mini-Mental State Examination (MMSE) evaluations were repeated every 6 months during a mean follow-up of 2 years. In AD patients, linear mixed models adjusted for age and sex were used to assess the cross-sectional and longitudinal associations between MMSE scores and baseline CSF levels of Aβ peptide (Aβ 1-42), Tau, phosphorylated Tau (p-Tau 181), PKR and pPKR. The mean (SD) MMSE at baseline was 20.5 (6.1) and MMSE scores declined over the follow-up (-0.12 point/month, standard error [SE] = 0.03). A lower MMSE at baseline was associated with lower levels of CSF Aβ 1-42 and p-Tau 181/Tau ratio. pPKR level was associated with longitudinal MMSE changes over the follow-up, higher pPKR levels being related with an exacerbated cognitive deterioration. Other CSF biomarkers were not associated with MMSE changes over time. In aMCI patients, mean CSF biomarker levels were not different in patients who converted to AD from those who did not convert.These results suggest that at the time of AD diagnosis, a higher level of CSF pPKR can predict a faster rate of cognitive decline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / psychology*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Cognitive Dysfunction / cerebrospinal fluid*
  • Cognitive Dysfunction / psychology*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid
  • eIF-2 Kinase / cerebrospinal fluid*
  • tau Proteins / cerebrospinal fluid

Substances

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

Grant support

This study was supported by Assistance publique hopitaux de Paris and Inserm. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.