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Abstract Details

Diagnostic Performance and Clinical Applications of a Commercial Alpha-synuclein Seed Amplification Assay in a Tertiary Care Memory Clinic
Aging, Dementia, and Behavioral Neurology
S1 - Alzheimer’s Disease and Related Dementias (2:48 PM-3:00 PM)
010

Assess the diagnostic performance of a commercially available seed amplification assay for pathologic alpha-synuclein (SAA) in patients with typical and rapid progressive dementia evaluated in a subspecialty memory clinic.
SAAs represent a promising biomarker of Lewy Body disease (LBD), with high sensitivity (87.3%, 95%CI: 0.755-0.947) and specificity (97.2%, 95%CI: 0.922-0.994) for detection of patients in the Parkinson’s Progression Markers Initiative repository with positive DaT SPECT; and reasonable sensitivity (78.7%, 95%CI: 0.66-0.88) and specificity (89.5%, 95%CI: 0.78-0.96 referencing clinical diagnoses in participants included within national research repositories. However, test performance in heterogeneous clinical cohorts is unknown. 

Patients with typical (n=122) and rapid progressive dementia (n=76) consented to banking of CSF at the time of clinically-indicated diagnostic lumbar puncture. Clinical data were deidentified and uploaded to a secure research database and clinical (etiologic) diagnoses established by two neurologists following independent review of available records. SAA (SYNTap™) were run on stored CSF by Amprion Diagnostics (San Diego, CA).

Median participant age was 69.1 years (18.4-86.1); 56.3% were female. CSF was sampled median 1.4 years (0-10.3) after symptom onset. Pathological alpha-synuclein was detected in 28/122 patients with typically progressive dementia (including 6/18 patients with presumed LBD; sensitivity 33%, specificity 79%) and 11/76 patients with rapid progressive dementia (including 3/9 patients with presumed LBD; sensitivity 33%, specificity 88%). “Positive” SAA was associated with tremor (OR=3.2, 95%CI: 1.3-7.8), visual hallucinations (OR=6.14, 95%CI 1.6-23.6), and REM behavior disorder (OR=3.7, 95%CI: 1.4-9.5) in patients with typical but not rapid progressive dementia. Brain autopsies were completed in 17 patients: Lewy bodies were detected in 2/3 patients with positive SAA and no patients with negative SAA.

“Positive” SAA demonstrated reasonable specificity but low sensitivity for the diagnosis of LBD. Additional studies in heterogeneous cohorts with neuropathologic data are needed to optimize clinical applications of SAA.
Authors/Disclosures
Amanda L. Porter, MD (Mayo Clinic)
PRESENTER 		Dr. Porter has nothing to disclose.
Christian Lachner Christian Lachner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PeerView.
Philip W. Tipton, MD Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AbbVie. Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Alzheimer's Tennessee. Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Charlotte County Medical Society, Inc.
Neill R. Graff-Radford, MD, FAAN (Mayo Clinic Jacksonville) The institution of Dr. Graff-Radford has received research support from Biogen. The institution of Dr. Graff-Radford has received research support from Lilly. The institution of Dr. Graff-Radford has received research support from Eisai. The institution of Dr. Graff-Radford has received research support from Biogen. Dr. Graff-Radford has received publishing royalties from a publication relating to health care.
Gregory S. Day, MD, MSc, FAAN (Mayo Clinic) Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Parabon Nanolabs. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vigil Neuro. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for DynaMed (EBSCO Health). Dr. Day has stock in ANI Pharmaceuticals. The institution of Dr. Day has received research support from National Institutes of Health / NIA. The institution of Dr. Day has received research support from Chan Zuckerberg Initiative. The institution of Dr. Day has received research support from Alzheimer's Association. The institution of Dr. Day has received research support from National Institutes of Health / NINDS. The institution of Dr. Day has received research support from Amgen Pharmaceuticals. The institution of Dr. Day has received research support from AVID Radiopharmaceuticals. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Presenter at Annual Meeting (CME) with 好色先生. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Content Development (CME) with PeerView, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Continuing 好色先生, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Ionis Pharmaceuticals. Dr. Day has a non-compensated relationship as a Clinical Director with Anti-NMDA Receptor Encephalitis Foundation that is relevant to AAN interests or activities.