Predicting brain amyloid load with digital and blood-based biomarkers

Abstract

Background: With the recent approval of anti-β-amyloid (Aβ) treatment for Alzheimer’s disease (AD), a demand has emerged for scalable, convenient and accurate estimations of brain Aβ burden for the detection of AD that would enable timely, accurate and reliable diagnosis in one’s primary care physician’s (PCPs) office as called for recently by World Health Organization (WHO). Methods: MemTrax, a 2-minute online memory test, was selected as the digital biomarker of cognitive impairment, and blood-based biomarkers (BBMs) including Aβ42, Aβ40, P-tau181, GFAP and NfL were used to estimate AD-related metrics in different groups of elderly individuals (n = 349) for comparison with Aβ PET scans of brain Aβ burden. The correlations between MemTrax, MoCA, BBMs and brain Aβ burden, expressed in centiloid (CL) values, were analyzed for predicting CL value alone or in combinations using machine-learning (ML). Results: Both MemTrax and the MoCA were able to differentiate Aβ status similarly. Integration of MemTrax and BBMs using ML, however, significantly improved the AUCs (over the same with MoCA) for differentiating Aβ status. MemTrax and p-Tau181/Aβ42 composite showed the strongest relationship with CL value among other BBMs. Most importantly, regression analyses of MemTrax and p-Tau181/Aβ42 aptly predicted CL values. Conclusion: The combination of MemTrax and BBMs provides an accurate, convenient, non-invasive, cost-effective and scalable way to estimate Aβ load, which provides an opportunity for mass screening and timely and accurate diagnosis of AD. Our findings could also facilitate more effective AD clinical management in the PCPs office worldwide for more equitable access to current standard of care.