Codon 129 polymorphism specific cerebrospinal fluid proteome pattern in sporadic Creutzfeldt-Jakob disease and the implication of glycolytic enzymes in prion-induced pathology.
Cerebrospinal fluid (CSF) contains a dynamic and complex mixture of proteins, which can reflect a physiological and pathological state of the central nervous system. In our present study, we show CSF protein patterns from patients with the two most frequent subtypes of sporadic Creutzfeldt-Jakob disease (sCJD) defined by the codon 129 genotype (MM, MV, and VV) and the protease-resistant form of prion protein (type 1 and type 2). The densitometric analysis of 2D gels showed up-regulation of 27 and down-regulation of 3 proteins in the MM-sCJD as well as the up-regulation of 24 proteins in the VV-sCJD as compared to nondemented control. Almost 40% of sCJD specific regulated proteins in CSF are involved in glucose metabolism, regardless of the codon 129 polymorphism. The increase in CSF levels of lactate dehydrogenase (LDH), glucose-6-phosphate isomerase (G6PI), and fructose-bisphosphate aldolase A (ALDOA) were validated on a larger group of sCJD patients including three possible codon 129 polymorphism carriers and three control groups consisting of nondemented, neurological cases as well as patients suffering from Alzheimer's disease or vascular dementia. Subsequently, the abundance of these glycolytic enzymes in the brain as well as their cellular localization were determined. This study demonstrates for the first time the implication of G6PI in prion-induced pathology as well as its cellular translocalization in sCJD. The identification of sCJD-regulated proteins in CSF of living symptomatic patients in our study can broaden our knowledge about pathological processes occurring in sCJD, as they are still not fully understood.
Gawinecka
Joanna
J
Department of Clinical Chemistry, Medical Center Georg-August University, Goettingen, Germany.
Dieks
Jana
J
Asif
Abdul R
AR
Carimalo
Julie
J
Heinemann
Uta
U
Streich
Jan-Hendrik
JH
Dihazi
Hassan
H
Schulz-Schaeffer
Walter
W
Zerr
Inga
I
D000368:Aged; D016022:Case-Control Studies; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D003062:Codon; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004798:Enzymes / Q000032:analysis*; D005786:Gene Expression Regulation; D006019:Glycolysis / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011328:Prions; D020543:Proteome / Q000032:analysis*
D003062:Codon; D004798:Enzymes; D011328:Prions; D020543:Proteome