Increased Cerebrospinal Fluid Levels of Double-Stranded RNA-Dependant Protein Kinase in Alzheimer's Disease

• Published in: Biological psychiatry (1969) Vol. 71; no. 9; pp. 829 - 835
• Main Authors: Mouton-Liger, François, Paquet, Claire, Dumurgier, Julien, Lapalus, Pauline, Gray, Françoise, Laplanche, Jean-Louis, Hugon, Jacques
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2012; Elsevier
• Subjects: Adult and adolescent clinical studies; Aged; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer Disease - enzymology; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; Biological and medical sciences; biomarkers; Biomarkers - cerebrospinal fluid; Case-Control Studies; Cell Line, Tumor; cerebrospinal fluid; Cognitive Dysfunction - cerebrospinal fluid; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - enzymology; Cognitive Dysfunction - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; eIF-2 Kinase - cerebrospinal fluid; Female; Geriatrics; Hippocampus - enzymology; Hippocampus - metabolism; Humans; Male; Medical sciences; Middle Aged; mild cognitive impairment; Nervous System Diseases - cerebrospinal fluid; Nervous System Diseases - diagnosis; Nervous System Diseases - enzymology; Nervous System Diseases - metabolism; Neurology; Organic mental disorders. Neuropsychology; Peptide Fragments - cerebrospinal fluid; Phosphorylation; PKR; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; ROC Curve; Sensitivity and Specificity; tau; tau Proteins - cerebrospinal fluid; tau; mild cognitive impairment; Alzheimer's disease; biomarkers; PKR; cerebrospinal fluid; Nervous system diseases; Cognitive disorder; Enzyme; Alzheimer disease; Transferases; Non-specific serine/threonine protein kinase; Biological marker; Cerebrospinal fluid; Cerebral disorder; Tau protein; Central nervous system disease; Degenerative disease
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2011.11.031

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. 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. 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. 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.