Archival ReportIncreased Cerebrospinal Fluid Levels of Double-Stranded RNA-Dependant Protein Kinase in Alzheimer's Disease
Section snippets
Patients
Between January 2010 and January 2011, 119 consecutive patients from our outpatient Memory Clinic who had a CSF analysis to explore cognitive impairment were included. We excluded, because of the small number, five subjects with lobar frontotemporal dementia or Lewy Body diseases and six patients with stroke or those who scored greater than 4 at the Hachinski Ischemic Scale and those with cardiovascular disease with consequences visible on brain magnetic resonance imaging (multiple large vessel
Results
Among the 108 included patients, 6 AD, 10 NDC, and 1 aMCI patients were excluded for technical reasons related to CSF assessment (8 for insufficient quantity of CSF; 9 for insufficient CSF protein concentration). These excluded patients were not different from included patients for age and sex ratio (Figure S1 in Supplement 1). A total of 91 patients were eventually enrolled in this study (AD, n = 45; aMCI, n = 11; NDC, n = 35). Neurological disease control patients were referred for cognitive
Discussion
Our results have revealed that pPKR and the ratio pPKR/T-PKR are increased in the CSF of AD patients compared with NDC. The sensitivity and the specificity of pPKR are 91.1% and 94.3%, respectively. In some AD patients whose CSF biomarker levels (Aß, T-tau, and p181tau) were not in the abnormal range, pPKR levels were abnormally high. These analyses were also abnormal in several MCI patients, but the small number of patients does not allow drawing, so far, any appropriate conclusions. A
References (38)
- et al.
The diagnosis of young-onset dementia
Lancet Neurol
(2010) - et al.
Revising the definition of Alzheimer's disease: A new lexicon
Lancet Neurol
(2010) - et al.
Research criteria for the diagnosis of Alzheimer's disease: Revising the NINCDS-ADRDA criteria
Lancet Neurol
(2007) - et al.
The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
Alzheimers Dement
(2011) - et al.
Beta amyloid in Alzheimer's disease: Increased deposition in brain is reflected in reduced concentration in cerebrospinal fluid
Biol Psychiatry
(2009) - et al.
Inverse association between CSF Abeta 42 levels and years of education in mild form of Alzheimer's disease: The cognitive reserve theory
Neurobiol Dis
(2010) - et al.
The dsRNA protein kinase PKR: virus and cell control
Biochimie
(2007) Endoplasmic reticulum stress and the inflammatory basis of metabolic disease
Cell
(2010)- et al.
Double-stranded RNA-dependent protein kinase links pathogen sensing with stress and metabolic homeostasis
Cell
(2010) - et al.
Upstream signaling pathways leading to the activation of double-stranded RNA-dependent serine/threonine protein kinase in beta-amyloid peptide neurotoxicity
J Biol Chem
(2003)
Activated double-stranded RNA-dependent protein kinase and neuronal death in models of Alzheimer's disease
Neuroscience
Activation of the cell stress kinase PKR in Alzheimer's disease and human amyloid precursor protein transgenic mice
Neurobiol Dis
Alzheimer's disease
Lancet
Activation of eukaryotic initiation factor-2 alpha-kinases in okadaic acid-treated neurons
Neuroscience
Double-strand RNA dependent protein kinase (PKR) is involved in the extrastriatal degeneration in Parkinson's disease and Huntington's disease
Neurochem Int
Classification and basic pathology of Alzheimer disease
Acta Neuropathol
Current concepts in mild cognitive impairment
Arch Neurol
The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics
Science
Apomorphine and Alzheimer Aβ: Roles for regulated α cleavage, autophagy, and antioxidation?
Ann Neurol
Cited by (0)
Authors FM-L, CP, and JD contributed equally to this work.