Scrapie and
bovine spongiform encephalopathy (BSE) are major global concerns and the emergence of
variant Creutzfeldt-Jakob disease (vCJD) has caused turmoil for
blood transfusion services and hospitals worldwide. Recent reports of iatrogenic CJD (iCJD) cases following
blood transfusions from
Transmissible Spongiform Encephalopathies (TSE)-infected donors have fuelled this concern. Major diagnostic tests for BSE and
scrapie are conducted post-mortem from animals in late stages of the disease. Although the lymphoreticular system is involved in the earlier pathogenesis of some forms of sheep
scrapie and vCJD, which presents great opportunity for diagnostic development, other TSE diseases (some strains of
scrapie,
sporadic CJD (sCJD) and bovine BSE) do not present such a diagnostic opportunity. Thus, there is an urgent need for pre-mortem tests that differentiate between healthy and diseased individuals at early stages of illness, in accessible samples such as blood and urine using less invasive procedures. This review reports on the current state of progress in the development and use of
prion and non-
prion biomarkers in the diagnosis of TSE diseases. Some of these efforts have concentrated on improving the sensitivity of PrPSc detection to allow in vivo diagnosis at low abundances of PrPSc whilst others have sought to identify non-
prion protein biomarkers of TSE disease, many of which are still at early stages of development. In this review we comment upon the limitations of
prion based tests and review current research on the development of tests for TSE that rely on non-
prion disease markers in body fluids that may allow preclinical disease diagnosis.