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Abstract Details

Performance of Alzheimer Disease Plasma Biomarkers in a Specialty Memory Clinic
Aging, Dementia, and Behavioral Neurology
S15 - Innovations in Alzheimer's Diagnostics (1:48 PM-2:00 PM)
005
Plasma measures of Aβ42/40 and pTau217 represent promising, accessible alternatives to “gold standard” metrics of cerebral amyloidosis in research cohorts; however, their performance in heterogeneous clinical cohorts is not yet established.
Evaluate the performance of emerging Alzheimer disease (AD) plasma biomarkers in a specialty memory clinic.

Plasma Aβ42/40 and pTau217 concentrations (Fujirebio Lumipulse) were measured in patients evaluated within a tertiary memory clinic. Syndromic and etiologic diagnoses were established by consensus, integrating clinical data and findings from MRI (n=484), FDG-PET (n=117), and CSF AD biomarkers (n=440). Performance of plasma biomarkers was evaluated using pre-established cutoffs optimized for prediction of amyloid pathology based on amyloid-PET.

Plasma AD biomarkers were measured in 509 patients (mean 68.6±9.3 years; 47% female; 91.3% non-Hispanic White), including patients with typical amnestic AD (n=235, 46.2%), non-amnestic presentations of AD (n=50, 9.8%), and non-AD causes of cognitive concerns (n=224, 44.0%). Positive plasma AD biomarkers were strongly associated with symptomatic AD (OR 95%CI; Aβ42/40≤0.0777: 3.8, 1.8-8.0; pTau217≥0.325 pg/mL: 25.0, 15.6-40.2) and CSF markers (elevated ptau181/Aβ42) of cerebral amyloidosis (Aβ42/40: 5.0, 1.7-14.3; pTau217: 42.4, 22.8-79.1). Using a 2 cutpoint model to classify results as positive, negative or intermediate; sensitivity, specificity, and predictive values (positive/negative) for plasma pTau217 were 95%, 85%, 87% and 92% when compared to AD diagnosis and 93%, 91%, 94% and 87% when compared to CSF AD biomarkers. Estimated glomerular filtration rate <60 mL/min/1.73 m2 associated with elevated plasma pTau217 in CSF AD-negative patients (mean difference, 95%CI: 0.265 pg/mL, 0.150-0.379).
Plasma ptau217, but not AB42/40, was strongly associated with symptomatic AD diagnoses and CSF AD biomarkers. These findings support the use of plasma ptau217 in heterogeneous clinical cohorts including patients with multiple common causes of dementia. Caution is advised in the interpretation of pTau217 results in patients with decreased renal function, due to potential elevations in plasma.
Authors/Disclosures
Yoav Piura, MD
PRESENTER 		Dr. Piura has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Piura has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck.
Christian Lachner Christian Lachner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PeerView.
Alicia Algeciras-Schimnich Alicia Algeciras-Schimnich has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Diagnostics. Alicia Algeciras-Schimnich has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Fujirebio Diagnostics. Alicia Algeciras-Schimnich has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche Diagnostics.
Daniel Figdore Daniel Figdore has nothing to disclose.
Joshua Bornhorst, PhD Prof. Bornhorst has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Roiche.
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.