title: Increased levels of cerebrospinal fluid JNK3 associated with amyloid pathology: links to cognitive decline.
abstract: BACKGROUND
  Alzheimer disease is characterized by cognitive decline, senile plaques of β-amyloid (Aβ) peptides, neurofibrillary tangles composed of hyperphosphorylated τ proteins and neuronal loss. Aβ and τ are useful markers in the cerebrospinal fluid (CSF). C-Jun N-terminal kinases (JNKs) are serine-threonine protein kinases activated by phosphorylation and involved in neuronal death.
  
  
  METHODS
  In this study, Western blots, enzyme-linked immunosorbent assay and histological approaches were used to assess the concentrations of Aβ, τ and JNK isoforms in postmortem brain tissue samples (10 Alzheimer disease and 10 control) and in CSF samples from 30 living patients with Alzheimer disease and 27 controls with neurologic disease excluding Alzheimer disease. Patients with Alzheimer disease were followed for 1-3 years and assessed using Mini-Mental State Examination scores.
  
  
  RESULTS
  The biochemical and morphological results showed a significant increase of JNK3 and phosphorylated JNK levels in patients with Alzheimer disease, and JNK3 levels correlated with Aβ42 levels. Confocal microscopy revealed that JNK3 was associated with Aβ in senile plaques. The JNK3 levels in the CSF were significantly elevated in patients with Alzheimer disease and correlated statistically with the rate of cognitive decline in a mixed linear model.
  
  
  CONCLUSIONS
  The study involved different samples grouped into 3 small cohorts. Evaluation of JNK3 in CSF was possible only with immunoblot analysis.
  
  
  CONCLUSIONS
  We found that JNK3 levels are increased in brain tissue and CSF from patients with Alzheimer disease. The finding that increased JNK3 levels in CSF could reflect the rate of cognitive decline is new and merits further investigation.
authors.affiliation: Institut du Fer à Moulin, Inserm UMR-S 839 and UMR-S 942, Lariboisière Hospital, the Department of Histology, Saint-Louis, Lariboisière, Fernand-Widal Hospital, AP-HP, University of Paris, Diderot, Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gourmaud
authors.affiliation: Institut du Fer à Moulin, Inserm UMR-S 839 and UMR-S 942, the Research Memory Centre, Paris Nord Ile de France, Saint-Louis, Lariboisière, Fernand-Widal Hospital, AP-HP, University of Paris, Diderot, and the Department of Histology, Saint-Louis, Lariboisière, Fernand-Widal Hospital, AP-HP, University of Paris, Diderot, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Paquet
authors.affiliation: Institut du Fer à Moulin, Inserm UMR-S 839 and UMR-S 942, the Research Memory Centre, Paris Nord Ile de France, Saint-Louis, Lariboisière, Fernand-Widal Hospital, AP-HP, University of Paris, Diderot, and the Department of Histology, Saint-Louis, Lariboisière, Fernand-Widal Hospital, AP-HP, University of Paris, Diderot, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Dumurgier
authors.affiliation: Institut du Fer à Moulin, Inserm UMR-S 839 and UMR-S 942, Lariboisière Hospital, Paris, France.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Pace
authors.affiliation: Department of Neuropsychiatry, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Constantin
authors.initials: C
authors.lastname: Bouras
authors.affiliation: Department of Pathology, Saint-Louis, Lariboisière, Fernand-Widal Hospital, AP-HP, University of Paris, Diderot, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Gray
authors.affiliation: Department of Biochemistry, Saint-Louis, Lariboisière, Fernand-Widal Hospital, AP-HP, University of Paris, Diderot, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Laplanche
authors.affiliation: Institut Pasteur, Hepacivirus and Innate Immunity Unit, Paris, France.
authors.forename: Eliane F
authors.initials: EF
authors.lastname: Meurs
authors.affiliation: Institut du Fer à Moulin, Inserm UMR-S 839 and UMR-S 942, Lariboisière Hospital, and the Department of Histology, Saint-Louis, Lariboisière, Fernand-Widal Hospital, AP-HP, University of Paris, Diderot, France.
authors.forename: François
authors.initials: F
authors.lastname: Mouton-Liger
authors.affiliation: Institut du Fer à Moulin, Inserm UMR-S 839 and UMR-S 942, Lariboisière Hospital, the Research Memory Centre, Paris Nord Ile de France, and the Department of Histology, Saint-Louis, Lariboisière, Fernand-Widal Hospital, AP-HP, University of Paris, Diderot, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Hugon
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000201:enzymology* / Q000473:pathology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000201:enzymology / Q000473:pathology; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D048057:Mitogen-Activated Protein Kinase 10; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8