J Psychiatry Neurosci. 2015 May;40(3):151-61.

Increased levels of cerebrospinal fluid JNK3 associated with amyloid pathology: links to cognitive decline.

 

Gourmaud S1, Paquet C2, Dumurgier J2, Pace C3, Bouras C4, Gray F5, Laplanche JL6, Meurs EF7, Mouton-Liger F8, Hugon J9.
  • 1Institut 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.
  • 2Institut 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.
  • 3Institut du Fer à Moulin, Inserm UMR-S 839 and UMR-S 942, Lariboisière Hospital, Paris, France.
  • 4Department of Neuropsychiatry, Geneva University Hospital, Geneva, Switzerland.
  • 5Department of Pathology, Saint-Louis, Lariboisière, Fernand-Widal Hospital, AP-HP, University of Paris, Diderot, France.
  • 6Department of Biochemistry, Saint-Louis, Lariboisière, Fernand-Widal Hospital, AP-HP, University of Paris, Diderot, France.
  • 7Institut Pasteur, Hepacivirus and Innate Immunity Unit, Paris, France.
  • 8Institut 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.
  • 9Institut 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.

 

 

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.

LIMITATIONS: The study involved different samples grouped into 3 small cohorts. Evaluation of JNK3 in CSF was possible only with immunoblot analysis.

CONCLUSION: 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.

PMID: 25455349

 

Supplements:

 

 

 

 

 

Multiselect Ultimate Query Plugin by InoPlugs Web Design Vienna | Webdesign Wien and Juwelier SchönmannMultiselect Ultimate Query Plugin by InoPlugs Web Design Vienna | Webdesign Wien and Juwelier Schönmann