Levels of CSF prostaglandin E2, cognitive decline, and survival in Alzheimer's disease

被引:84
作者
Combrinck, M
Williams, J
De Berardinis, MA
Warden, D
Puopolo, M
Smith, AD
Minghetti, L
机构
[1] Ist Super Sanita, Dept Cell Biol & Neurosci, Sect degenerat & Inflammatory Neurol Dis, I-00161 Rome, Italy
[2] Univ Dept Pharmacol, Oxford Project Invest Memory & Ageing, Oxford, England
[3] Radcliffe Infirm, Oxford OX2 6HE, England
关键词
D O I
10.1136/jnnp.2005.063131
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: Although epidemiological, clinical, and experimental evidence indicates that the inducible isoform of cyclooxygenase (COX-2) may be involved in the pathogenesis of several neurodegenerative disorders, the mechanisms whereby COX-2 contributes to Alzheimer's disease are largely unknown. Objective: To undertake a longitudinal study of CSF levels of a major product of COX activity, prostaglandin E-2 (PGE(2)), in relation to cognitive decline and survival in patients with Alzheimer's disease. Methods: CSF PGE(2) was measured on at least three annual visits in 35 controls and 33 Alzheimer patients ( 26 necropsy confirmed) who completed the Cambridge cognitive assessment (CAMCOG). Results: Compared with controls, CSF PGE(2) was higher in patients with mild memory impairment, but lower in those with more advanced Alzheimer's disease. The median survival time of patients with higher initial PGE(2) levels was five years longer than those with lower levels. Conclusions: COX activity in Alzheimer's disease varies with stage of the disease. PGE(2) levels correlate positively with patient survival. These findings suggest that inhibition of COX activity does not represent a major target for the pharmacological treatment of Alzheimer's disease.
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页码:85 / 88
页数:4
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