Prediction of Cerebral Amyloid Pathology Based on Plasma Amyloid and Tau Related Markers

Background and Purpose: Pyroglutamate-modified β-amyloid peptide (Aβ pE ) is crucial for AD pathophysiological process. The potential associations of plasma Aβ pE and total tau (t-tau) with brain Aβ burden and cognitive performance remain to be clarified. Methods: Forty-six subjects with unimpaired cognition, mild cognitive impairment, or very mild dementia were enrolled. Plasma levels of Aβ pE3−40 , t-tau, and Aβ42 were quantified by immunomagnetic reduction (IMR) assays. We analyzed individual and combined biomarker correlations with neuropsychological scores and Aβ positivity determined by 18 F-florbetapir positron emission tomography (PET). Results: Both plasma Aβ pE3−40 levels and Aβ pE3−40 /t-tau ratios correlated negatively with short-term memory and global cognition scores, while correlating positively with PET standardized uptake value ratios (SUVRs). Among the biomarkers analyzed, the combination of Aβ pE3−40 in a ratio with t-tau had the best discriminatory ability for Aβ PET positivity. Likewise, logistic regression analysis showed that Aβ pE3−40 /t-tau was a highly robust predictor of Aβ PET positivity after controlling for relevant demographic covariates. Conclusion: Plasma Aβ pE3−40 /t-tau ratios correlate with cognitive function and cerebral Aβ burden. The suitability of Aβ pE3−40 /t-tau as a candidate clinical biomarker of AD pathology in the brain should be examined further in larger studies.