Elucidating factors affecting blood levels of tau and GFAP in adults at risk for neurodegeneration

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In this supplemental project, we will gain insights into tau and GFAP as biomarkers for Alzheimer’s disease (AD) and related dementias (ADRDs) by leveraging ultrasensitive blood assays. Ultrasensitive blood tests are emerging as valuable tools to achieve several milestones set by the National Institute on Aging to advance urgently needed treatments for AD and ADRD. While multiple biomarkers show differences in median levels between AD patients versus controls, no single biomarker thus far can reliably diagnose or prognose individual patients. Clinical interpretation of individual tests remains complicated due to overlap between AD and non-AD groups. A biofluid signature for AD, which uses an algorithm to analyze data for multiple biomarkers, promises to significantly advance ultrasensitive blood tests as translatable biomarkers for diagnosis and prognosis. Here, a collaboration between Meso Scale Diagnostics, LLC. (MSD) and Kaiser Permanente will analyze specimens from the Kaiser- Permanente Research Biobank to study determinants and statistical distribution of tau and GFAP in a community-based population typical of the intended population for AD screening. These insights are critical to developing diagnostic algorithms for ethnically diverse, mixed- gender populations that span a large age range. In particular, we will determine complex cut- points for biomarkers influenced by age, gender, and ethnicity. We will develop and assess a mathematical model for biomarker distributions that can be incorporated into diagnostic and prognostic algorithms. Finally, we will explore root causes for unusually elevated plasma levels of tau and GFAP among individuals without cognitive complaints, which pose a significant challenge for interpreting biomarker concentrations.