Abstract Details

Title The National Prion Disease Pathology Surveillance Center’s Experience and Diagnostic Accuracy of CSF RT-QuIC for Diagnosing Prion Disease in a Large Autopsy Confirmed Sample

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S13 - Behavioral and Cognitive Neurology: Behavioral Neurology, Aging, and Dementia (2:17 PM-2:28 PM)

Poster/Presentation
Number 008

Background Prion diseases are rapidly progressive and invariably fatal neurodegenerative diseases. RT-QuIC is a protein conformation amplification assay that detects the presence of disease-causing prion protein. The clinical performance of RT-QuIC, including the assay’s sensitivity and specificity, as well as characteristics that may influence the results, require further investigation.

Objective In this prospective study, the sensitivity and specificity of cerebrospinal fluid (CSF) real-time quaking induced conversion (RT-QuIC) for the diagnosis of prion disease was evaluated by comparing antemortem RT-QuIC results with definitive autopsy findings.

Design/Methods From May 2015 to April 2018, the National Prion Disease Pathology Surveillance Center (NPDPSC) tested RT-QuIC, total tau, and 14-3-3 on CSF from 10,551 living patients suspected of having prion disease, of which 560 subsequently had autopsy completed by the Center as of October 2018. Neuropathologic examination at autopsy was used as the gold-standard comparator for this study.

Results The sensitivity and specificity of RT-QuIC in this cohort of 560 individuals with prion disease was 89.6% (441/492) and 99% (67/68), respectively. One false positive result was found in a patient with multifactorial dementia (vascular and Alzheimer's disease). The sensitivity in sporadic CJD (sCJD) was 90.7% (410/452), and the sensitivity in genetic prion disease was 78% (31/40). Sixty-seven percent (28/42) of sCJD cases that had negative RT-QuIC results had elevated total tau levels (>1150 pg/ml) and four cases of sCJD had low tau (<500 pg/ml) and negative RT-QuIC.

Conclusions CSF RT-QuIC demonstrates good sensitivity and is the most specific antemortem diagnostic test for prion disease. Most instances of false negative RT-QuIC have elevated levels of tau, but some cases of prion disease do not yield abnormal CSF laboratory results. The sample bias of autopsy attainment is a limitation of this study as cases sent to the NPDPSC for neuropathologic examination are suspected of having prion disease.

Authors/Disclosures
Brian Appleby, MD (University Hospitals Case Medical Center) PRESENTER	Dr. Appleby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Appleby has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Ionis. Dr. Appleby has received personal compensation in the range of $0-$499 for serving as a Consultant for Sangamo. The institution of Dr. Appleby has received research support from CJD Foundation. The institution of Dr. Appleby has received research support from Ionis. The institution of Dr. Appleby has received research support from Alector. The institution of Dr. Appleby has received research support from CDC. The institution of Dr. Appleby has received research support from NIH. Dr. Appleby has received publishing royalties from a publication relating to health care. Dr. Appleby has received publishing royalties from a publication relating to health care.
	No disclosure on file
	No disclosure on file
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Mark Cohen	Mark Cohen has nothing to disclose.
	No disclosure on file

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