Prions: Appleby, Rhoads et al.

Update on the National Prion Disease Pathology Surveillance Center

Brian S Appleby1,2, Daniel R Rhoads1,3, Aaron Foutz1, Danielle Jordan1, Mark L Cohen1,3
1National Prion Disease Pathology Surveillance Center, Case Western Reserve University
2Departments of Neurology and Psychiatry, Case Western Reserve University and University Hospitals Cleveland Medical Center
3Department of Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center

Background: Prion diseases (e.g. Creutzfeldt-Jakob disease, CJD) are rapidly progressive neurodegenerative conditions that are characterized by rapidly progressive dementia, myoclonus, and cerebellar, visual, and extrapyramidal symptoms.  Three etiologies can cause CJD: sporadic, genetic, and acquired.  The Centers for Disease Control and Prevention (CDC) fund the National Prion Disease Pathology Surveillance Center (NPDPSC) to assist in tracking the incidence and to determine the etiology of human prion diseases in the U.S.  Among current concerns is the question of whether or not chronic wasting disease (CWD), a prion disease of cervids (e.g., deer, elk), can be transmitted to humans.

Methods:  The NPDPSC has an autopsy program that will coordinate and pay for autopsies of suspected prion disease cases from across the country.  Histopathology, prion protein typing, and genotyping are performed at the NPDPSC and results are sent to clinicians.  Genetic testing of the prion protein gene (PRNP) can be conducted on brain tissue or blood of living patients.  Cerebrospinal fluid (CSF) of suspected cases can also be sent to the NPDPSC for testing of 14-3-3 and tau proteins, as well as for real-time quaking induced conversion (RT-QuIC), which detects abnormal seeding activity of the disease causing prion protein.  The NPDPSC also has a brain magnetic resonance imaging (MRI) consultation program. 

Results:  The NPDPSC coordinates approximately 400 autopsies per year, 70% of which are confirmed to be prion disease.  Close to 4,000 CSF samples were analyzed last year and preliminary analyses demonstrate that clinicians may be more likely to ask for an autopsy when cases are positive for RT-QuIC. Over the last 20 years, only four cases of variant CJD have been identified in the U.S., all of which are most likely to have been acquired outside of the U.S.  No cases of CWD transmission to humans have been demonstrated to date.  

Conclusions:  The NPDPSC is an important resource for the CDC, human prion disease surveillance, and clinicians.  Autopsy remains the gold standard for prion disease diagnosis, and perhaps more importantly, to determine the etiology of prion disease.  Autopsy is more important than ever given the rising threat of CWD in the U.S.