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Abstract Details

Analytical and Clinical Assessment of Plasma Phospho-Tau Isoforms in Alzheimer’s Disease (AD)
Aging, Dementia, Cognitive, and Behavioral Neurology
S15 - Innovative Diagnostics in Dementia (2:00 PM-2:12 PM)
006

Highly phosphorylated Tau protein is a major component of neurofibrillary tangles, a primary AD neuropathological cortical marker.  Recently, sensitive immunoassays capable of measuring p-Tau isoforms p-Tau217 and p-Tau181 in blood have been developed, with promising diagnostic potential for AD.  

Evaluate the analytical and clinical performance of four p-Tau assays using plasma from AD subjects and healthy controls, and determine correlative and discriminatory relationships for each assay and clinical diagnosis group.

AD plasma (n=64) and healthy control plasma (n=25) were analyzed with Simoa p-Tau217 developed by Alzpath, p-Tau181V2 and p-Tau181V2.1 (Quanterix) immunoassays using the HD-X analyzer, and the Lumipulse p-Tau181 (Fujirebio) immunoassay using the G1200 system. Plasma p-Tau levels were evaluated within AD sample groups consisting of mild (n=16, MMSE >23-30), moderate (n=20, MMSE=16-22) and severe (n=28, MMSE<16) cognitive impairment, and healthy controls (n=25).  

P-tau levels were detectable by the four assays in >95% of all samples.  Analysis by the three p-Tau181 and one p-Tau217 assays revealed significant increases in median p-Tau levels in the combined AD group (2.5-4.4-fold; p<0.0001, n = 64), relative to controls (n=25), and group discrimination (ROC-AUC=0.92). Significant median p-Tau elevations of 2.8-8.5 fold were observed in the moderate and severe dementia groups (p <0.0001) and 1.3-1.8 fold in the mild dementia group (p=0.0001-0.003), although distributions overlapped.  Moderate or severe dementia group discrimination from controls was more pronounced (AUC>0.95) compared to mild dementia (AUC=0.75-0.84).  Moderate to strong correlations between the p-Tau levels measured by the four assays were observed (Pearson r = 0.7-0.9).

All p-Tau measurements were significantly elevated in the plasma of mild, moderate, and severe AD groups. All four p-Tau assays demonstrated robust analytical performance, and clinically differentiated AD plasma from healthy control plasma (p<0.0001).  Plasma p-Tau181 and p-Tau217 biomarkers provide a practical diagnostic opportunity to identify AD patients.

Authors/Disclosures
Ahmed Chenna, PhD (Monogram Biosciences Inc)
PRESENTER
Dr. Chenna has received personal compensation for serving as an employee of LabCorp-monogram Biosciences.
Andreas Jeromin, PhD (Quanterix Corp.) Dr. Jeromin has received personal compensation for serving as an employee of AlzPath, Inc. Dr. Jeromin has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Quanterx.
Brandon C. Yee (Monogram Biosciences/LabCorp) Mr. Yee has received personal compensation for serving as an employee of Monogram Biosciences/LabCorp. Mr. Yee has stock in LabCorp.
Youssouf Badal Youssouf Badal has nothing to disclose.
Muriel Joy Mendes, Other (Bristol Myers Squibb) Mrs. Mendes has nothing to disclose.
Christos John Petropoulos, PhD (Monogram Biosciences, LabCorp) Dr. Petropoulos has received personal compensation for serving as an employee of Monogram Biosciences-Labcorp. Dr. Petropoulos has received stock or an ownership interest from Laboratory Corporation of America Holdings. Dr. Petropoulos has received intellectual property interests from a discovery or technology relating to health care.
John Winslow, PhD (Monogram Biosciences Inc., Laboratory Corporation of America) Dr. Winslow has received personal compensation for serving as an employee of Monogram Biosciences/Labcorp. Dr. Winslow has stock in Labcorp. Dr. Winslow has received intellectual property interests from a discovery or technology relating to health care.