A brain killer kinase in Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder marked by memory troubles and cognitive
deficits. With senile plaques and neurofibrillary tangles, neuronal loss and inflammation are the
major hallmarks of the disease. The cause of neuron death is not solved but it is a clear target for
new treatments. A team from Lariboisière Hospital, led by Pr Hugon (AP‐HP ‐ University Paris 7 ‐
Inserm unit 839) in Paris France has just revealed that a potent killer enzyme, PKR (Protein Kinase R),
was activated and circulating in the brain and cerebrospinal fluid (CSF) of AD patients. Their work, for
which a patent has been applied by AP‐HP, has just been published in the journal Biological
Psychiatry (*)

Once activated by phosphorylation, PKR leads to cellular death by apoptosis, can trigger
inflammation and impairs memory formation. This team has found that the level of activated PKR
was three time higher in the CSF of AD patients as compared to non AD patients. PKR was also
elevated in the CSF of a group of patients with Mild Cognitive Impairment, an early phase of AD. In
addition, activated PKR levels were correlated with those of phosphorylated tau levels, an existing
CSF AD biomarker. This study reveals that PKR could be, at the same time, a potent and early
mediator of impaired memory and neuronal death in AD, an actor of inflammatory processes and a
possible new CSF biomarker. PKR represents a new therapeutic target to slow down AD progression
and modify the inexorable decline of cognitive functions in affected patients.
“The kinase PKR is implicated in several degenerative processes detected in the brain of patients with
Alzheimer's Disease, explains Pr Hugon. New researches are underway to attenuate its functions by
new specific "kinase inhibitors" that could represent a powerful way to attenuate memory deficits in
AD patients”

About the OTT&PI of AP‐HP

The Assistance Publique‐Hôpitaux de Paris (AP‐HP) is the University medical center of the Paris‐Ile de
France region. In this respect, it provides comprehensive medical care while running the research
and teaching projects that will shape the medicine of the future. The group is comprised of 37
hospitals (including 3 outside Paris) and a home care organization.


* Biol Psychiatry. 2012 Jan 24 ‐ Increased Cerebrospinal Fluid Levels of Double‐Stranded RNADependant
Protein Kinase in Alzheimer's Disease. Mouton‐Liger F, Paquet C, Dumurgier J, Lapalus P,
Gray F, Laplanche JL, Hugon J; for the Groupe d'Investigation du Liquide Céphalorachidien Study