CJD Diagnostic Tests
The ANCJDR provides routine diagnostic testing services to aid the assessment of suspected sporadic, familial and iatrogenic TSE cases nationwide and, as required, to New Zealand and South-East Asian countries. These include the CSF 14-3-3 protein Western Blot test and vCJD testing for PrPres using tonsil biopsies.
Testing cerebrospinal fluid (CSF)
The 14-3-3 protein is an ante-mortem, non-specific marker of central nervous system neuronal injury or death. Based on international experience in carefully selected patients, a positive result has approximately 90% sensitivity and specificity for sporadic Creutzfeldt Jakob disease. False positives are recognized in various disease processes; for example encephalitis, encephalopathies and recent cerebral infarcts. Unselected sampling is consequently less reliable if the 14-3-3 protein CSF test is used to screen for a possible diagnosis of CJD.
In February 2010, evaluation of all 2002-2008 Australian CSF referrals where a known clinical outcome was provided to the ANCJDR after detailed follow-up revealed a test sensitivity of 88.5% and specificity of 87.6%.
- No less than 1 ml of CSF – PLEASE DO NOT SPIN SAMPLE.
- CSF samples are to be packaged into polypropylene, sterile tubes with no additives.
- Double bag, freeze and transport frozen on dry ice. You are responsible for organizing your courier service to pick up and deliver the sample to The Florey Institute.
- Please provide routine cell counts and protein levels. These data are required for interpretation of the test result.
- A copy of the original request slip and a completed specimen data sheet have to accompany the sample. Please provide accurate billing details in your referral documents.
- PLEASE NOTIFY REGISTRY STAFF THAT THE SAMPLE IS BEING SENT.
Information about the test
- The test is run weekly.
- Samples received by 4pm Friday will have the result issued by the end of the following week.
- A researcher from the ANCJDR will contact the treating clinician directly to clarify clinical details.
- Positive and medically significant results are verbally reported to the requesting clinician within 24-48 hours.
- All test results are faxed to the referring laboratory.
A typical 14-3-3 western blot
Unsuitable samples will not be tested. All samples are screened on receipt and those considered unsuitable will be disposed of. The referring clinician will be contacted upon receipt of such a sample and advised. A report will be issued. An unsuitable sample will include the following:
- Macroscopically haemorrhagic samples
- Xanthochromic samples
- Red blood cell counts >500 cells per µl
- White cell counts >10 cells per µl
- Spun supernatants
Based on cumulative experience and published results, these samples are unsuitable to test due to the 14-3-3 protein existing in erythrocytes, platelets and plasma. Lysis of these cells releases the protein thus contaminating the CSF sample and giving a false positive result. (Day I.N.M and Thompson R.J. Clinica Chimica Acta 1984; 136: 219-228, Collins et al, J Clin Neurosci 2000; 7:203-208).
Specimen Data Sheet
This form must accompany specimens sent for testing (download specimen data sheet - [PDF 180KB; updated 01/11/2018). The PDF document contains form fields allowing for completion of some or all fields prior to printing.
Domestic samples incur a non-rebatable fee of $ AUD150.00
International samples incur a fee of $AUD300.00
Total Tau in CSF ELISA assay
NATA/RCPA Accreditation No. 19256
The measurement of total Tau in CSF is partially complementary to 14-3-3 protein detection for supporting the diagnosis of sporadic CJD. Similar to 14-3-3 protein, levels of total Tau protein within the CSF are a non-specific markers of neuronal injury. The measurement of CSF Tau by ELISA has been standardized and extensively studied for its utility in supporting a diagnosis of Alzheimer’s disease when used in conjunction with amyloid-β1-42 and phospho-tau. In addition, CSF Tau has demonstrated valuable sensitivity and specificity for ante-mortem diagnosis of CJD.
The cut-off value for CJD is 1072 pg/ml, providing 85% sensitivity and 82% specificity. False positives are recognized in various disease processes; for example encephalitis, encephalopathies and recent cerebral infarcts. Consequently, unselected sampling is less reliable as screening for a possible diagnosis of sporadic CJD.
Reference link: CSF Tau supplements 14-3-3 protein detection for sporadic Creutzfeldt–Jakob disease diagnosis while transitioning to next generation diagnostics
The sample must be collected directly into the polypropylene tube
Specimen Data Sheet
This form must accompany specimens sent for testing (download specimen data sheet - updated 14/06/2018). The PDF document contains form fields allowing for completion of some or all fields prior to printing.
Total Tau protein in CSF incurs a non-rebatable fee of $ AUD 150.00
The Tau assay is performed as a NATA accredited diagnostic test at the National Dementia Diagnostic Laboratories
The RT-QuIC assay measures the presence of misfolded prion protein in the patient’s CSF with reported specificity approximately 99% and sensitivity ranging from ~80-95%.
RT-QuIC is currently performed at the ANCJDR on research basis only, following evaluation with the treating clinician, and is transitioning to offering RT-QuIC as a routine diagnostic test. Please contact the ANCJDR on 03 8344 1949.
Reference: Ultrasensitive human prion detection in cerebrospinal fluid by real-time quaking-induced conversion. Nature Medicine VOLUME 17 | NUMBER 2 | FEBRUARY 2011 p. 175-178
Biopsy testing involves testing a sample of tonsil (fresh and fixed) tissue for evidence of prion disease (Protease-resistant PrP).
Codon 129 testing
Codon 129 testing involves testing of DNA extracted from tissue or blood samples to determine the Codon 129 polymorphism.
Please contact the ANCJDR before collecting tissue biopsies for instructions and requirements.
Domestic samples do not incur a fee.
International samples incur a fee of $ AUD 600.00
Only the investigation of the whole brain after death can provide a definite diagnosis of whether or not the individual had prion disease; it provides the family and clinicians with the highest level of confidence in the diagnosis of the patient. When a differential diagnosis includes CJD full body autopsies cannot be offered due to infection control reasons.
A brain only autopsy, where the whole brain is examined, is voluntary and depends entirely on informed consent from the Senior Available Next of Kin (SANOK). The treating doctor is expected to educate the patient’s family about benefits and disadvantages of the autopsy, as if undertaking any other routine medical procedure. Consent for an elective autopsy is documented by the requesting doctor and SANOK signing an autopsy consent form.
As CJD brain only autopsies assist public health surveillance of CJD in Australia and contribute to the knowledge base and research of CJD, there is no additional cost to the family or referring institution for any aspect of the autopsy.
Reporting of the neuropathology results may take between three to twelve months and may vary from state to state. The neuropathology report is issued to the diagnosing and referring clinicians. The doctor is requested to communicate the result to the patient’s family.
Unfixed brain tissue also preserves a sample of the patient’s DNA, which can be used at a later stage for PRNP testing. Brain tissue from neuropathology confirmed CJD patients is stored indefinitely at the ANCJDR while the ANCJDR is operating. There is no cost associated with the storage of the brain tissue; extraction of DNA from brain tissue incurs a fee of $ 200.
Contact details by State
Nationally: Christiane Stehmann, ANCJDR coordinator (03 8344 1949)
VIC: The Alfred, mortuary (03 9076 2684)
TAS: Royal Hobart Hospital, mortuary (03 6222 8333)
NSW/ACT: DOFM Glebe (02 8584 7820)
QLD: Royal Brisbane and Women’s Hospital, mortuary (07 3646 8041)
SA: Royal Adelaide Hospital, mortuary (08 8222 4894 or 08 8222 3295)
WA: Fiona Stanley Hospital, mortuary (08 6152 5218)
NT: Royal Darwin Hospital, Centre of Disease Control (08 8922 8510)
Family members can contact the coordinator of the ANCJDR (03 8344 1949) or the CJD Support Group network (1800 052 466) for information, assistance and support.
Approximately 10-15% of prion disease occurs due to an inherited genetic fault (mutation). Mutations in a gene called the prion protein gene (PRNP) can lead to Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS) and fatal familial insomnia (FFI). Approximately one in ten million people have such a PRNP mutation.
The PRNP test is a genetic test, where DNA from an individual is analysed for the presence of mutations associated with genetic prion diseases. DNA can be extracted from blood or unfixed autopsy tissue (preferably brain) for the purpose of testing.
It is recommended to store extracted DNA from a blood sample for every suspected CJD patient in order to secure the option of future genetic testing for the patient’s family. This allows the patient’s family the option to consider PRNP testing of their relative at a later stage. Taking a blood sample for long-term storage of DNA is optional.
Genetic testing is entirely voluntary. PRNP testing is frequently requested when a family history of prion disease or concerns for a genetic basis are raised. These tests are often referred by the treating clinician to confirm the aetiology of the disease (genetic or not) to assist in patient care. In cases where there is no family history it is advisable to defer genetic testing until a neuropathology report is available, if a neuropathological confirmation of prion disease was requested.
Testing for genetic prion disease often raises significant medical, ethical, psychological and legal issues for living blood relatives. In the majority of cases, PRNP testing will be consented by next-of-kin due to cognitive impairment of the patient or because the patient is deceased. It is therefore advised that consent is recorded in a written document. Consultation with a genetic service is recommended in general, especially because of the implications if a mutation is detected in the PRNP gene. Further, the results of a PRNP test are not always straightforward, which often makes them challenging to interpret and explain. Also, a family history is not always known including through misdiagnosis of previous cases in the family.
At least 5 mls EDTA blood marked for ‘DNA extraction and storage for possible future prion protein gene testing for a patient with suspected CJD or other prion disease’ or ‘PRNP testing’.
Storage and testing location
Department of Diagnostic Genomics
PathWest Laboratory Medicine WA
Level 2, PP Building
QEII Medical Centre
Nedlands WA 6009
Phone: +61 8 6383 4219
Fax No.: +61 8 9346 4029
DNA extraction from autopsy brain tissue (stored at the ANCJDR) and transfer to the testing laboratory incurs a fee of $ 200.00.
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