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Increased cerebrospinal fluid levels of double-stranded RNA-dependant protein kinase in Alzheimer's disease.
Biol Psychiatry 2012; 71(9):829-35BP

Abstract

BACKGROUND

The pathological hallmarks of Alzheimer's disease (AD) include accumulation of amyloid-β (Aβ) 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), Aβ 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 Aβ, 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+Show Affiliations

Memory Clinical Center, Lariboisiere Fernand Widal Saint Louis Hospital, Assistance Publique -Hôpitaux de Paris, University of Paris Diderot, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22281122

Citation

Mouton-Liger, François, et al. "Increased Cerebrospinal Fluid Levels of Double-stranded RNA-dependant Protein Kinase in Alzheimer's Disease." Biological Psychiatry, vol. 71, no. 9, 2012, pp. 829-35.
Mouton-Liger F, Paquet C, Dumurgier J, et al. Increased cerebrospinal fluid levels of double-stranded RNA-dependant protein kinase in Alzheimer's disease. Biol Psychiatry. 2012;71(9):829-35.
Mouton-Liger, F., Paquet, C., Dumurgier, J., Lapalus, P., Gray, F., Laplanche, J. L., & Hugon, J. (2012). Increased cerebrospinal fluid levels of double-stranded RNA-dependant protein kinase in Alzheimer's disease. Biological Psychiatry, 71(9), pp. 829-35. doi:10.1016/j.biopsych.2011.11.031.
Mouton-Liger F, et al. Increased Cerebrospinal Fluid Levels of Double-stranded RNA-dependant Protein Kinase in Alzheimer's Disease. Biol Psychiatry. 2012 May 1;71(9):829-35. PubMed PMID: 22281122.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased cerebrospinal fluid levels of double-stranded RNA-dependant protein kinase in Alzheimer's disease. AU - Mouton-Liger,François, AU - Paquet,Claire, AU - Dumurgier,Julien, AU - Lapalus,Pauline, AU - Gray,Françoise, AU - Laplanche,Jean-Louis, AU - Hugon,Jacques, AU - ,, Y1 - 2012/01/26/ PY - 2011/07/08/received PY - 2011/11/16/revised PY - 2011/11/16/accepted PY - 2012/1/28/entrez PY - 2012/1/28/pubmed PY - 2012/8/14/medline SP - 829 EP - 35 JF - Biological psychiatry JO - Biol. Psychiatry VL - 71 IS - 9 N2 - BACKGROUND: The pathological hallmarks of Alzheimer's disease (AD) include accumulation of amyloid-β (Aβ) 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), Aβ 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 Aβ, 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. SN - 1873-2402 UR - https://www.unboundmedicine.com/medline/citation/22281122/Increased_cerebrospinal_fluid_levels_of_double_stranded_RNA_dependant_protein_kinase_in_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-3223(11)01212-1 DB - PRIME DP - Unbound Medicine ER -