High-throughput proteomics using submicroliter amounts of plasma for comprehensive assessment of the immune status

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Summary The SARS-CoV-2 pandemic of 2020 vastly affected normal clinical and research operations. The negative impact is particularly severe on studies involving older adults given the high risk for severe COVID-19 disease, where the mean/median age of deceased COVID-19 patients is >80 years of age. Due to these unique circumstances, the years `20 and `21 will result in `lost years' for many longitudinal studies that involve older adults as it is too risky for participants to leave the safe environment of their home for e.g. a blood draw. A loss of two years of sampling is particularly damaging for longitudinal studies involving older adults including the NIA-funded BIOCARD Study started in 1995 which has prospectively followed >300 cognitively normal middle-aged participants in an effort to understand the pathogenesis of Alzheimer's disease (AD) and its relationship with aging. This well characterized cohort undergoes detailed annual neuropsychologic testing and blood collection with biannual MRI, PET and CSF collection for understanding the molecular basis of AD. The challenge is to ensure the safety of these subjects without compromising data collection. One possibility is to use NoviPlex cards for the safe at home collection of blood samples. However, only 2.5ul of plasma can be collected – with current proteomics methods, this amount of plasma cannot yield a deep quantitative data set. We hypothesize that integrating at home sample collection strategies using the NoviPlex cards and state-of-the- art sample-sparing analyses strategies being developed by the Steen Lab (U24AI152179: High-throughput proteomics using submicroliter amounts of plasma for comprehensive assessment of the immune status) will allow the safe collection of samples and data from vulnerable patients during the current COVID-19 pandemic. We propose that our platform will facilitate high quality data acquisition on small plasma volumes collected at home in a quick and easy manner. Such an integrated sample-sparing collection and analysis strategy will allow researchers to continue collecting useful plasma samples from participants of the BIOCARD study despite the ongoing COVID-19 pandemic during this critical phase of BIOCARD where a substantive portion of the participants are manifesting cognitive symptoms of AD given their advanced age. To test our hypothesis, we will compare the proteome of venous vs. microcapillary (i.e. NoviPlex card) plasma (Specific Aim 1) and collect microcapillary plasma remotely from active participants in the longitudinal BIOCARD study (Specific Aim 2). This proposal for an administrative supplement will add an AD focus on the existing U24 from Dr. Steen, which currently focuses on sample sparing plasma proteomic assays. The requested supplement will allow us to establish an innovative approach facilitating remote collection of microcapillary plasma and high-quality data in 2021 from high-risk participants of the unique BIOCARD study. Furthermore, this home sampling strategy will enable plasma sample collection with a much higher temporal resolution than currently feasible and financially viable, which is of significant interest for a wide range of longitudinal studies.