Elevation of 12/15 lipoxygenase products in AD and mild cognitive impairment.
The 12/15 lipoxygenase (12/15LOX) enzyme is increased in pathologically affected frontal and temporal regions of Alzheimer's disease (AD) brains compared with controls. Herein, we measured 12(S)-HETE and 15(S)-HETE levels, products of 12/15LOX, in cerebrospinal fluid (CSF) of normal individuals, subjects with mild cognitive impairment (MCI) and AD. Compared with controls, there was a significant increase of both metabolites in CSF from AD and MCI, which correlated with lipid peroxidation and tau protein levels. These results suggest that the activation of this enzyme occurs early in the course of AD, before the onset of overt dementia, thereby implicating 12/15LOX-mediated lipid peroxidation in the pathogenesis of AD.
Yao
Yuemang
Y
Department of Pharmacology, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA.
Clark
Christopher M
CM
Trojanowski
John Q
JQ
Lee
Virginia M-Y
VM
Praticò
Domenico
D
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000134:cerebrospinal fluid; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000201:enzymology / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D001092:Arachidonate 12-Lipoxygenase / Q000134:cerebrospinal fluid*; D001093:Arachidonate 15-Lipoxygenase / Q000134:cerebrospinal fluid*; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000201:enzymology / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000134:cerebrospinal fluid; D008297:Male; D013223:Statistics as Topic; D016875:tau Proteins / Q000134:cerebrospinal fluid
D001057:Apolipoproteins E; D006893:Hydroxyeicosatetraenoic Acids; D016875:tau Proteins; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase