Alzheimer Plasma Biomarkers Distinguish SuperAgers from their Cognitively Average Peers

Abstract

AbstractBackgroundSuperAgers are individuals ≥80 years old who were selected for having episodic memory performance that is at least as good as individuals 20‐30 years their junior. We have previously shown that on average SuperAgers show lower neurofibrillary tangle density in the entorhinal cortex than cognitively average controls, which may be one biological factor contributing to superior memory beyond the 8th decade. This preliminary study investigated whether plasma concentrations of Alzheimer and related neurodegenerative biomarkers differ between SuperAgers and their cognitively average peers.MethodSuperAgers (N = 61) and Cognitively Average Controls (N = 28) were enrolled through the SuperAging Research Program. The plasma biomarkers amyloid β peptide 40 (Aβ40), amyloid β peptide 42 (Aβ42), neurofilament light (NFL), phosphorylated tau‐181 (pTau‐181), and glial fibrillary acidic protein (GFAP) were measured in SuperAgers and Cognitively Average participants using the Quanterix single molecule protein detection (SIMOA) platform. Independent samples t‐tests were used for statistical analyses (significance was set at p<0.05, uncorrected).ResultThere were no significant differences in mean age between SuperAgers and Cognitively Average Controls. Concentrations of Aβ42, Aβ40, the ratio of Aβ42/Aβ40, NFL or GFAP did not significantly differ between groups. On average, SuperAgers and Controls showed pTau‐181 levels that were <16.5 pg/mL, falling within the “Unlikely Alzheimer’s” designation according to Quanterix guidelines. SuperAgers showed significantly lower pTau‐181 levels compared to Cognitively Average Controls [M = 5.42 pg/mL (SD = 2.60) vs M = 7.10 pg/mL (SD = 3.14), respectively].ConclusionPlasma phosphotau biomarkers are promising for the assessment of brain integrity versus degeneration across the age‐Alzheimer continuum. The current results provide preliminary support for the contention that the SuperAger brain may be even more removed from the Alzheimer side of the continuum than neurotypical controls.Emily Rogalski and Changiz Geula contributed equally to this study.