2005 Fiscal Year Final Research Report Summary
Detection of Proteinase K resistant prion protein for an early diagnosis of Creutzfeldt-Jakob disease
| Project/Area Number |
16590810
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | TOHOKU UNIVERSITY |
|---|
Principal Investigator |
SHIGA Yusei TOHOKU UNIVERSITY, TOHOKU UNIVERSITY HOSPITAL, LECTURER, 病院, 講師 (90271931)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Keywords | prion disease / Creutzfeldt-Jakob disease / Proteinase K / urine / early diagnosis / diffusion-weighted MRI / PrP^<Sc> |
|---|
| Research Abstract |
Creutzfeldt-Jakob disease (CJD) is a fatal and transmissible encephalopathy, and its therapy has not established yet. An early diagnosis of CJD had been beneficial for public hygiene, however, it is also beneficial for CJD patients themselves because therapeutic trials are starting. In the present diagnostic criteria, pathological detection of protainase K resistant prion protein (PrP^<Sc>) is needed for a diagnostic of definite CJD, i.e., we need post mortem examination or biopsy. We have no non-invasive methods of the diagnosis. A few years ago, it was reported that PrPSc was detected in urine of CJD patients and experimental model of CJD. We estimated the reliability of protainase K resistant prion protein (PrP^<Sc>) in the urine of CJD patients using monoclonal antibody against prion protein, 3F4 and 6H4. We detected PrP^<Sc> in urine of CJD patients, but it was not specific for CJD patients. We also detected "PrP^<Sc>" in urine small number of patients with central nervous system
… More
(CNS) diseases other than CJD.
We also examined a relationship between "PrP^<Sc>" detection in urine and proteinuria and we did not detect "PrP^<Sc>" in urine of patients with proteinuria without CNS disease. There was no relationship between detection of "PrPSc" in urine and proteinuria. It was also reported that "PrP^<Sc>" in urine did dot have infectivity. Our results also showed that detected "PrP^<Sc>" in urine did not show molecular shift when treated with proteinase K These findings were very unusual if "PrP^<Sc>" detected in urine was real PrP^<Sc>. Therefore, we hypothesized that "PrPSc" detected in urine was not real PrPSc, and that normal PrP was converted to "PrPSc" during the process detecting "PrP^<Sc>', mainly dialysis of urine. We tried detection of "PrP^<Sc>" using normal PrP, but it failed. Recently other group reported that "PrP^<Sc>' detected in urine was not real PrPSc, it was outer membrane of bacteria in urine.
We also examine other clinical markers such as periodic synchronous discharges in EEG, 14-3-3 protein and tau protein in the cerebrospinal fluid, and diffusion-weighted MRI findings for a diagnosis of CJD and compared the diagnostic reliability with "PrP^<Sc>" in urine. At present, diffusion-weighted MRI is the most reliable diagnostic marker for an early diagnosis of CJD. Less
|
