Abstract Details

Title CSF PKR Is a Diagnostic and Prognostic Marker in Alzheimer's Disease

Topic Aging and Dementia

Presentation(s) IN3 - (-)

Poster/Presentation
Number 005

Objective

Background In AD, histological hallmarks include senile plaques , neurofibrillary tangles made of hyperphosphorylated tau protein and synaptic and neuronal losses. In AD, the A? 1-42 cerebrospinal fluid (CSF) levels are decreased whereas , CSF tau and phosphorylated tau (pTau) are increased . PKR, a pro-apoptotic kinase controling protein synthesis, is activated by virus, cytokines, calcium, viruses and A? 1-42. PKR can modulate inflammation, levels of BACE 1 and A? 1-42 production as well as tau phosphorylation. The genetic knock down of PKR improves memory in experimental mice. In this study we have tried to determine if CSF levels of PKR and activated PKR (pPKR) could be modified in AD patients compared to neurological controls and serve as a prognostic marker.

Design/Methods Fourty five AD patients, 11 patients with Mild Cognitive Impairment and 35 neurological controls were prospectivelly included and followed for more than 2 years . All patients had initially, a lumbar puncture to determine the CSF levels of A? 1-42, Tau and pTau and the concentrations of PKR and pPKR using western blot procedures. Cognitive evaluation was performed twice a year. All patients or care giver gave their written inform consents.

Results The mean CSF pPKR level was increased by 300% in AD patients compared to neurological controls. The sensitivity was 91.1% and the specificity was 94.3%. pPKR concentrations were also increased in the majority of MCI patients. In AD patients PKR and pPKR levels correlate with pTau levels and with the cognitive decline assessed with repeated MMSE over the 2 years-period.

Conclusions The evaluation of CSF PKR and pPKR concentrations could help to improve AD diagnosis and could be an appropriate prognostic marker in AD patients.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Claire Paquet (Hopital Lariboisiere)	No disclosure on file
	No disclosure on file

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