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 ¹⁸F-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.