期刊
BIOLOGICAL PSYCHIATRY
卷 71, 期 9, 页码 829-835出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2011.11.031
关键词
Alzheimer's disease; biomarkers; cerebrospinal fluid; mild cognitive impairment; PKR; tau
资金
- Inserm
- Assistance Publique-Hopitaux
- Novartis
Background: The pathological hallmarks of Alzheimer's disease (AD) include accumulation of amyloid-beta (A beta) peptide forming extracellular senile plaques, neurofibrillary tangles made of hyperphosphorylated tau protein with neuronal loss. A beta 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 A beta 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), A beta 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 A beta, 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.
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