PIB-PET AS A STANDARD FOR EVALUATING THE CLINICAL ACCURACIES OF DIAGNOSING ALZHEIMER’S DISEASE WITH CLINICAL DIAGNOSIS AND PLASMA BIOMARKERS

Abstract

Recent advances in quantifying plasma beta-amyloid and total tau protein (T-Tau) by using immunomagnetic reduction (IMR) technology provide the possibilities of early or preclinical diagnosis of Alzheimer's pathology. Latest findings of two parameters, plasma Ab1–42/Ab1–40 and Ab1–42xT-Tau, showed high accuracy (>80%) with clinical diagnosis by NIA-AA 2011 criteria and guidelines. Amyloid PET image is also a biomarker-based tool that widely used for early and preclinical diagnosis. But little evidence is shown for the correlation between plasma biomarkers and amyloid PET image. Here, 19 older control participants, 16 participants with MCI due to AD, and 19 AD patients, who were diagnosed according to NIA-AA 2011 guidelines, were enrolled for measuring plasma Ab1–40, Ab1–42 and T-Tau proteins. All participants received 11C-labeled Pittsburgh compound B PET (PiB-PET) scans. A cutoff value to define PET-positive or PET-negative group was determined by binary analysis of total standard uptake value ratios (SUVR-total) in the frontal, parietal, temporal lobes, ACC and the precuneus. The cutoff value for differentiating PET-positive from PET-negative in terms of SUVR-total is 7.0. By using the SUVR-total of 7.0 as a diagnostic standard, 94.7% of older controls are PET-negative, 56.3% of 16 subjects with MCI due to AD are PET-positive, and 84.2% of AD patients are PET-positive. Through ROC-curve analysis, the cutoff value of plasma Ab1–42/Ab1–40 ratio to discriminate PET-positive from PET-negative subjects is found to be 0.370, which corresponds 80.8% and 78.4 % for sensitivity and specificity. The area under curve is 0.868.