Search NASA⌕ Search

SEARCH · Search NASA

Results for “Barrier risks”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2

Advanced Transmission Technologies (ATTs) Supplier Cohort Workshops Cohort Summary [Slides]

This Summary slide deck summarizes the key outcomes of the Advanced Transmission Technologies (ATTs) supplier cohort, part of Idaho National Laboratory’s (INL) Technical Assistance for Digital Assurance (TADA) program. The program aimed to strengthen grid resilience through cybersecurity controls, supply-chain security, and Cyber-Informed Engineering (CIE) for advanced transmission technologies. The cohort brought together vendors representing the full range of Grid-Enhancing Technologies (GETs), including providers of Dynamic Line Ratings (DLR), Advanced Power Flow Control (APFC), Transmission Topology Optimization (TTO), and High-Performance Conductors (HPCs). Discussions focused on institutional, integration, and operational barriers limiting GET adoption; cybersecurity risks at EMS/SCADA, cloud, and network integration points; and supply-chain transparency issues such as semiconductor dependence and SBOM/HBOM expectations. Participants also addressed operator trust, human-in-the-loop requirements, and challenges with utility adoption, while exploring how CIE can support secure deployment of GETs. This deck represents a consolidated summary of challenges and risks identified by vendors, cross-cutting themes and technology-specific insights from three cohort workshops, and actionable mitigations to guide utilities, vendors, and the Department of Energy in advancing secure, trusted deployment of GETs.

24 - POWER TRANSMISSION AND DISTRIBUTION↗

Resilient buildings for fire-adapted landscapes: EE and flexible loads integrated with solar and storage microgrids

Energy efficiency (EE) and flexible loads can be part of a resilient buildings packagewhen they are combined with solar and storage in a clean energy microgrid to reduce the carbonfootprint of buildings and enable resilience to extreme events. Recent large wildfires and an emerging understanding of the fire-adapted landscapes in the American West underscore the urgency of work towards scaling and commercializing these systems. For example, a recent power shutoff in Northern California (October 9-12, 2019) resulted in 738k customers disconnected at the peak of the outage and is emblematic of challenges to come. Our paper reports on insights from a clean energy microgrid deployment pilot that integrates a 50 kWAC PV array, a 109 kW / 174 kWh battery system, switchgear to safely isolate from the regional power system, and communicating controllers for HVAC and refrigeration. The project will be commissioned in May 2020 and is sited at a critical infrastructure site in rural Northern California – in this case a gasoline station with convenience store. Our experience and results shed light on capabilities of integrated microgrids to provide value to customers during blue sky conditions and resilience during black sky days with high fire risk, and what opportunities and barriers exist for scaling these integrated microgrid systems in the near term. We use a simulation model to estimate how EE and flexibility can extend the run time of solar and storage, improving the reliability of power at critical sites.

Alstone, Peter↗

Less-Than-Lethal Quick Deploy Inflatable Hall/Door Barrier: VISTA Feasibility Study

Physical protection of public buildings has long been a concern of police and security services where a balance of facility security and personnel safety is vital. Due to the nature of public spaces, the use of permanently installed and deploy-on-demand physical barrier systems must be safe for the legitimate occupants and visitors of that space. Such systems must seek to mitigate the personal and organizational consequences of unintentionally seriously injuring or killing an innocent bystander by slamming a heavy, rigid, and quick-deploying barrier into place. Consideration and implementation of less-than-lethal technologies is necessary to reduce risk to visitors and building personnel. One potential barrier solution is a fast-acting, high-strength, composite airbag barrier system for doorways and hallways to quickly deploy a less-than-lethal barrier at entry points as well as isolate intruders who have already gained access. This system is envisioned to be stored within an architecturally attractive selectively frangible shell that could be permanently installed at a facility or installed in remote or temporary locations as dictated by risk. The system would be designed to be activated remotely (hardwired or wireless) from a Central Alarm Station (CAS) or other secure location.

42 ENGINEERING↗

Unlocking the Path to Decarbonized Building Thermal Systems: Strategies for Designers and Contractors: Preprint

The design and construction community plays a pivotal role in facilitating the transition to decarbonized thermal systems that maintain human comfort while reducing building emissions. Through the U.S. Department of Energy Better Buildings initiative's Design and Construction Allies, a cohort of leading architecture, engineering, and construction firms have identified top ranked barriers that designers and contractors face when implementing solutions for building owners. These barriers to decarbonizing thermal - especially heating - systems include equipment availability; electrical capacity constraints; space allocations; complex system configurations; and lack of experience in designing, installing, and maintaining heat pumps. These impediments significantly amplify the risk and financial burden associated with the adoption of decarbonized solutions. The barriers also decrease the likelihood that designers, contractors, and owners will adopt decarbonization strategies without clear plans and guidance on how to implement these solutions, mitigate risk, and overcome the identified barriers. The National Renewable Energy Laboratory, the Design and Construction Allies, and the American Society of Heating, Refrigerating, and Air-Conditioning Engineers have developed "how to" thermal decarbonization guidance based on best practices. The subjects covered range from the role of energy efficiency in facilitating decarbonized heating solutions to strategies for decarbonizing new and existing heating, ventilating, and air-conditioning systems. The focus is on overcoming barriers so that energy-efficient, electrified buildings - both new and retrofit - become the industry standard. This paper outlines 1) the method used to collect and organize this guidance, 2) industry barriers to decarbonization, and 3) decarbonization techniques that have broad market applicability.

building heating↗

A Community Guide to Regulatory Barriers Affecting Microgrids (Reports 1-3)

In response to growing risks of power outages from extreme weather and aging infrastructure, communities are increasingly exploring the potential of microgrids to provide reliable energy access. Microgrids offer promising solutions to meet this challenge but face a complex landscape of non-technical barriers, particularly regulations concerning the provision and distribution of energy. Most existing legal and regulatory frameworks were designed for a centralized, one-way power system, and are often poorly suited to handle systems that independently balance distributed energy resources with local load. This three-part report series provides a strategic analysis of existing regulatory and legal factors affecting microgrid deployments to help non-technical community leaders and decision-makers better understand the feasibility of a microgrid in their community. -Report No. 1: Foundational Issues Facing Microgrids details the universal policy barriers all microgrids face, including utility interconnection processes, rate structures, and local permitting. -Report No. 2: Single Property Microgrids outlines how direct asset ownership and operating behind-the-meter can bypass some regulatory oversight, using the Blue Lake Rancheria microgrid as a case study. -Report No. 3: Multi-Property Microgrids tackles the complex challenges of crossing public rights-of-way and navigating utility franchise rights, highlighting the Coventry microgrid project. The series equips decision-makers with phased frameworks to navigate financial and regulatory complexities, engage effectively with local utilities and Authorities Having Jurisdiction (AHJs), and structure successful microgrid projects.

24 POWER TRANSMISSION AND DISTRIBUTION↗

Dataset for report: Non-Technical Barriers to Geothermal Development in California and Nevada

In California and Nevada, geothermal projects are subject to non-technical barriers, which may create development delays leading to higher project costs and risks and decreased competitiveness with other electricity generation technologies. These non-technical barriers may include federal and state permits, authorizations, environmental reviews, and other regulatory requirements that are applicable throughout different phases of geothermal project development. The 2022 National Renewable Energy Laboratory (NREL) report, "Non-Technical Barriers to Geothermal Development in California and Nevada" presents findings of a study on non-technical barriers that may influence geothermal project development. The set of data resources relied upon for the report includes: 1) interviews conducted with relevant geothermal stakeholders including regulators and project developers, 2) federal and state environmental review documents developed for specific projects, 3) a techno-economic analysis conducted using the NREL Annual Technology Baseline (ATB) framework, and 4) an analysis of the impacts of site-specific land access and permitting considerations on project development readiness conducted using the Geothermal Resource Portfolio Optimization and Reporting Technique (GeoRePORT) Socioeconomic Assessment Tool (SEAT).

15 GEOTHERMAL ENERGY↗

Book Chapter: Small Modular Reactors

Small Modular Reactors (SMRs) have been a very promising development in nuclear power over the last two decades. SMRs are defined as nuclear reactors with a power output of less than 300 MWe. This is in comparison to gigawatt-size reactors, which can have electrical output of 1000–1500 MWe or more. This chapter will consist of two major sections. The first will be a detailed summary of the small modular reactor designs being proposed around the world. This section will focus on those that are the furthest along in their development, but will also include some information about the wide variety of proposed designs that require significant research and development. The second part will be a discussion of the remaining challenges to the adoption of SMRs as a major energy source. SMRs are not a new concept, but they do represent a new vision for an older concept. These reactors have the potential to become a major source of energy in the near future. The development of small, modular designs can help promote the adoption of nuclear energy by reducing upfront costs, reducing the financial risk associated with nuclear power, and the barriers to entry. However, the adoption of SMRs is not without challenges. Regulatory and licensing changes to address the unique benefits and concerns associated with SMRs will continue to be a challenge as regulators adapt to the unique features emerging from the design process. The development of new instrumentation and control systems is an ongoing issue. And economics is possibly the most significant challenge, with high construction costs, cheap natural gas, and government subsidies, combining to result in significant financial risk associated with adopting nuclear generation.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

Immediate effects of acute Mars mission equivalent doses of SEP and GCR radiation on the murine gastrointestinal system-protective effects of curcumin-loaded nanolipoprotein particles (cNLPs)

Introduction: Missions beyond low Earth orbit (LEO) will expose astronauts to ionizing radiation (IR) in the form of solar energetic particles (SEP) and galactic cosmic rays (GCR) including high atomic number and energy (HZE) nuclei. The gastrointestinal (GI) system is documented to be highly radiosensitive with even relatively low dose IR exposures capable of inducing mucosal lesions and disrupting epithelial barrier function. IR is also an established risk factor for colorectal cancer (CRC) with several studies examining long-term GI effects of SEP/GCR exposure using tumor-prone APC mouse models. Studies of acute short-term effects of modeled space radiation exposures in wildtype mouse models are more limited and necessary to better define charged particle- induced GI pathologies and test novel medical countermeasures (MCMs) to promote astronaut safety. Methods: In this study, we performed ground-based studies where male and female C57BL/6J mice were exposed to γ-rays, 50 MeV protons, or 1 GeV/n Fe-56 ions at the NASA Space Radiation Laboratory (NSRL) with histology and immunohistochemistry endpoints measured in the first 24 h post-irradiation to define immediate SEP/GCR-induced GI alterations. Results: Our data show that unlike matched γ-ray controls, acute exposures to protons and iron ions disrupts intestinal function and induces mucosal lesions, vascular congestion, epithelial barrier breakdown, and marked enlargement of mucosa-associated lymphoid tissue. We also measured kinetics of DNA double-strand break (DSB) repair using gamma-H2AX- specific antibodies and apoptosis via TUNEL labeling, noting the induction and disappearance of extranuclear cytoplasmic DNA marked by gamma-H2AX only in the charged particle-irradiated samples. We show that 18 h pre-treatment with curcumin-loaded nanolipoprotein particles (cNLPs) delivered via IV injection reduces DSB-associated foci levels and apoptosis and restore crypt villi lengths. Discussion: These data improve our understanding of physiological alterations in the GI tract immediately following exposures to modeled space radiations and demonstrates effectiveness of a promising space radiation MCM.

59 BASIC BIOLOGICAL SCIENCES↗

Ready for Renewables: Grid Planning and Competitive Renewable Energy Zones (CREZ) in the Philippines

The Department of Energy of the Philippines launched the competitive renewable energy zones (CREZ) process to help achieve the country's goals of scaling up renewable energy generation on the power system and to ensure sustainable, secure, reliable, accessible, and affordable energy. The CREZ process identifies the most economic renewable energy resource areas so transmission planning and expansion can accelerate their development. By proactively focusing transmission expansion to these resource areas, renewable energy generation development obstacles such as transmission access, energy curtailment, land permitting (such as protected or high-slope areas), and regulatory barriers are easier to overcome thus, reducing risk for private sector renewable energy investment. This report is will cover the outputs of the CREZ process, the development of the outputs through stakeholder-driven coordination, and how this process will help the Philippines achieve their renewable energy goals.

24 POWER TRANSMISSION AND DISTRIBUTION↗

RRFMC Drop Tester: Conduct of R&D Engineering System Risk Assessment

This report provides a documented risk assessment and subsequent determination of engineering rigor for the modification of the drop tester system inside of the Respirable Release Fraction Measurement Chamber (RRFMC) located in TA03-130. This risk assessment does not apply to the modification of the structural support system, containment barrier, pressure system, nor fluid system of the RRFMC, but only seeks to address the risk associated with the specific system used to raise and drop test articles.

42 ENGINEERING↗

Assessment of Potential Ergonomic Injury Risk in the Nuclear Material Processing Glovebox Environment [Capstone Project]

Gloveboxes are isolation barriers that are used within many different industries such as pharmaceuticals, electronic parts fabrication, nuclear, and biological. The research on glovebox ergonomics is currently limited with few ergonomic professionals that focusing exclusively on glovebox working environments. There is existing documentation on occupational injuries, such as musculoskeletal disorders (MSD), sustained as a direct result of working in gloveboxes. The main elements that pose ergonomic risks to glovebox workers are operational repetition, duration, force, vibration, lifting heavy (more than 15lbs with two hands) objects, and awkward postures. This paper examines a small sample of the potential causal or risk factors that lead to the ergonomic injuries. A meta-analysis utilizing a random effect model is used to examine data from several studies which focus on, dexterity and strength changes as result of glove thickness, and robotic assistive technology as a means to improve postural mechanics. With the meta-analysis technique, similar data sets from different research studies can be coalesced into a single weighted, statistically significant result for subsequent consideration. The results from the analysis show that increased glove thickness results in decreased dexterity for operators thus increasing ergonomic risk factors such as task duration. It is also shown that glove thickness decreases grip strength but a similar decrease in pinch strength is not definitively demonstrated. With decreased grip strength, operators will need to exert more force (a known ergonomic risk factor) on processing tools, etc. during operations thus increasing the risk of ergonomic injury. The use of robotic assistive technology as a means to improve operator posture (risk factor) was also examined. Although it may be intuitively assumed that human-robotic collaboration would be beneficial in reducing risk factors, the result from this study’s analysis was not statistically significant. It is inferred that with additional directed research on this topic another study/analysis could be statistically significant demonstrating the benefits of the technology.

99 GENERAL AND MISCELLANEOUS↗

Nontechnical Barriers to Geothermal Development

Geothermal energy presents a significant opportunity for the United States (US). The US has the largest known geothermal resource in the world, with over 31 GW of conventional geothermal (i.e., hydrothermal) potential. Despite this, the development of geothermal power plants has lagged other renewable resources. Though some of the gaps stem from technical barriers numerous non-technical barriers are preventing geothermal energy from reaching its full potential. The gaps include a need to reduce the cost impacts of seismic risk, environmental risk, exploration, drilling and permitting cost risk, and reduced summer capacity on plant profitability. This report identifies pathways to overcome these barriers. We find that geothermal energy could increase its market presence by acting as a complement to lower cost renewables, providing flexible or baseload power in low carbon scenarios. We also outline several contractual and operational strategies (including the use of hybrid systems) that plant operators can pursue to improve the value of their resource, such as multi part remuneration mechanisms that guarantee revenue (e.g., availability payments or a Contract for Differences approach) or resource risk hedging approaches (e.g., shaped market products and portfolio resource approaches).

15 GEOTHERMAL ENERGY↗

Development of an Assessment Methodology That Enables the Nuclear Industry to Evaluate Adoption of Advanced Automation

Nuclear power has a crucial role in providing safe, reliable, and economical carbon-free electricity for today and the future. For continued operation, many of the existing United States nuclear power plants will begin the subsequent license renewal process for extending their operating license periods. As plants extend their expected operating lifetimes, there is a significant opportunity to modernize. These plants have a much stronger business case with these extended mission periods to modernize and significantly enhance their economic viability in current and future energy markets by implementing digital technologies that support innovation, efficiency gains, and business-model transformation. Ensuring continued safety and reliability is crucial. Transformative digital technologies—including automation—that fundamentally change the concept of operation for the nuclear power plant operating model requires a critical focus on the human and technology integration element. Further, the nuclear industry has historically been reluctant to modernize due to having a risk adverse culture and lack of clarity for a transformative new state vision (Joe & Remer, 2019; Thomas et al., 2020). Common barriers include (1) the perceived value and return on investment (ROI) of digital technology, (2) the perceived risk associated with licensing, regulatory, and cybersecurity, and (3) insufficient guidance for performing digital modifications to power generation systems. This work presents a methodology to address these barriers and support the industry in adopting advanced automation and digital technology through developing a transformative vision and implementation strategy that will address the human and technology integration element. This research leverages previous LWRS Program and industry results. It draws specifically on previous LWRS Program research in the areas of advanced alarm systems, computer-based procedures, model informed decision support, and advanced human-system interface displays (e.g., overviews and task-based). The modernization methodology can be used to guide transformative thinking when integrating a set of vendor-specific capabilities to support a new concept of operations and a utility’s end-state vision. The results of this research are organized into six major sections: - Section 1 introduces the need for supporting large-scale digital modifications that will renew the technology base for extended operating life beyond 60 years - Section 2 describes the challenges that the nuclear industry is enduring with modernizing. - Section 3 summarizes the primary standards and guidance. - Section 4 presents earlier work from the LWRS Program regarding the development of a transformative conceptual design for an advanced control room of a hybrid plants. - Section 5 presents a methodology that is designed at addressing the challenges in the industry today in achieving a transformative new state vision and concept of operations. - Conclusions and next steps of this research are provided in Section 6.

99 GENERAL AND MISCELLANEOUS↗

Development of Stable Solid Oxide Electrolysis Cells for Low-Cost Hydrogen Production

The project objective was to demonstrate a solid oxide cell-based steam electrolysis stack that exhibits robustness, reliability, endurance, hydrogen purity, and produces hydrogen at elevated pressure of 2 to 3 bar. Innovative materials and processing methods were evaluated to improve degradation characteristics. Performance improvement focused on nearly all layers involved in the cell and stack assembly. Primary attention was paid to zirconia-ceria interface resistance control via sintering optimization and decrease in degradation from the oxygen electrode by evaluating low strontium (Sr) or Sr-free composition for both the oxygen electrode and current collection layer. Stack robustness was addressed by validating redox tolerance of fuel electrode, confirming capability of cells to survive repeated thermal cycles, studying the effect of pressure on performance and degradation, evaluating the effect of contamination on fuel and oxygen electrode performance and degradation, and identifying mitigation strategies to improve performance. The characterization included evaluation of electrochemical performance and stability followed by microstructural analysis. At the cell level, performance and stability improvements were achieved by incorporating a Sr-free oxygen electrode and a denser oxygen electrode barrier layer. At the stack level, pressurized operation reduces demand on first stage compression, the redox tolerant fuel electrode mitigates risk from service interruptions, and improvements to interconnect coating alleviate chromium (Cr) contamination effects. The denser barrier layer was achieved by adding a sintering aid to the samaria-doped ceria (SDC) composition that reduced sintering temperature by 150 °C. The resulting density was on par with the baseline SDC barrier layer density and the lower sintering temperature resulted in less resistive phase formation during sintering. Button cell tests did not demonstrate a change in performance when exposed to silicon (Si) or manganese (Mn) impurities to the fuel electrode and Cr impurity to the oxygen electrode. More detailed study however is warranted. The project addressed SOEC performance and stability at the cell and stack levels through a systematic approach to known sources of degradation that were combined and tested in three stack tests using an electrolyte supported cell design to allow for evaluation of a variety of fuel and oxygen electrode compositions. STK-82 and STK-83 had identical compositions. STK-100 incorporated the best materials and processing variables developed under this and concurrent projects, and was tested at elevated pressure in steam electrolysis. • STK-82 recovered performance after redox and thermal cycling, demonstrating the robustness of the stack and seals. It exhibited stable performance in testing for 500 hours in SOEC mode, followed by 300 hours of cycling between SOEC and SOFC tests. Degradation during SOEC operation was 1.8 %/ 1,000 hours. • STK-83 generated hydrogen at >80% steam conversion, and oxygen above 98.5 % purity during pressurized operation. Both hydrogen and oxygen were generated at 3 barg pressure without the use of a pressure vessel. In addition to balanced pressure, electrolysis operation at 1 bar differential pressure across anode and cathode was also demonstrated to substantial the robustness of the cell and seal. • STK-100 measured at initial ambient pressure conditions showed an area specific resistance of 1.1 ohm-cm 2 , and STK-83 had 1.3 ohm-cm 2 .

08 HYDROGEN↗

Perceptions of Seasonal Influenza Vaccine Among U.S. Army Civilians and Dependents in the Kaiserslautern Military Community: A Mixed-Methods Survey

ABSTRACT Introduction Influenza is a globally occurring viral respiratory infection that can lead to hospitalizations and death. An influenza outbreak can interfere with combat readiness in a military setting, as the infection can incapacitate soldiers. Vaccination remains the most effective tool to prevent and mitigate seasonal influenza. Although influenza vaccinations for U.S. Army soldiers can be monitored through military health systems, those systems cannot capture DoD civilians and Army dependents who may not use military health services. This study aims to gauge flu vaccine uptake and perceptions in U.S. Army civilians and dependents. Materials and Methods An online survey was e-mailed to civilian and dependent enrollees of Landstuhl Regional Medical Center. The survey contained 24 questions pertaining to demographics, vaccine history, history of the flu, and beliefs toward vaccines. Chi-square tests, t-tests, and logistic regressions were performed to investigate the association between demographic, behavior, and belief factors with vaccine uptake. Free-text answers were coded and categorized by themes. Results Over 70% of respondents were vaccinated for the flu. There were differences between vaccinated and unvaccinated respondents regarding their perceptions of barriers to vaccination, benefits of the flu vaccine, severity of flu symptoms, and personal risk of getting ill with the flu. After controlling for confounders, flu vaccination in the previous season and healthcare worker status were associated with increased vaccine uptake, while perceived barriers to influenza vaccination were associated with decreased vaccine uptake. Conclusions Flu vaccine uptake may be increased by increasing access to vaccination, promoting vaccination and addressing concerns at the provider level, and engaging positively framed public messaging. Increasing flu vaccine uptake is of particular importance as the flu season approaches during the COVID-19 (Coronavirus disease 2019) pandemic.

Burns, MSC, Veronica M.↗

Strategic Qualitative Risk Assessment of Thousands of Legacy Wells within the Area of Review (AoR) of a Potential CO2 Storage Site

The subsurface confinement of anthropogenic carbon dioxide (CO2) demands robust risk assessment methodologies to identify potential leakage pathways. Legacy wells within the Area of Review (AoR) represent one potential leakage pathway. Robust methodologies require enormous amounts of data, which are not available for many old legacy wells. This study strategically categorizes 4386 legacy wells within the AoR of a potential CO2 storage site in the Illinois basin and identifies the high-risk wells by leveraging publicly available data—reports and well logs submitted to state regulatory agencies. Wells were categorized based on their proximity to the injection well location, depth, the mechanical integrity of well barriers, and the accessibility to these wells throughout the project lifecycle. Wells posing immediate risks were identified, guiding prioritized corrective actions and monitoring plans. Out of 4386 wells, 54 have high priority for corrective action, 10 have medium priority, and the remainder are of low priority. Case study results from the Illinois basin demonstrate the effectiveness and applicability of this approach, to assess the risk associated with legacy wells within the AoR of potential CO2 storage site, strategically categorizing over 4000 such wells despite data limitations.

Arbad, Nachiket (ORCID:0000000215353656)↗

Proactive Regulatory Approaches to Electrification and Load Growth: Pre-read Document to Support the July 10-11 th Workshop

This document summarizes objectives and context related to a DOE-funded workshop on proactive regulatory approaches to electrification and load growth. It briefly summarizes some of the regulatory barriers to pursuing a proactive approach and some of the risks associated with such an approach. It then summarizes a selection of recent utility proposals and public utility commission actions related to proactive approaches.

24 POWER TRANSMISSION AND DISTRIBUTION↗

Variants in the MS4A cluster interact with soluble TREM2 expression on biomarkers of neuropathology

Recent evidence suggests that Alzheimer’s disease (AD) genetic risk variants (rs1582763 and rs6591561) of the MS4A locus are genome-wide significant regulators of soluble TREM2 levels such that the minor allele of the protective variant (rs1582763) is associated with higher sTREM2 and lower AD risk while the minor allele of (rs6591561) relates to lower sTREM2 and higher AD risk. Our group previously found that higher sTREM2 relates to higher Aβ 40 , worse blood–brain barrier (BBB) integrity (measured with the CSF/plasma albumin ratio), and higher CSF tau, suggesting strong associations with amyloid abundance and both BBB and neurodegeneration complicate interpretation. We expand on this work by leveraging these common variants as genetic tools to tune the interpretation of high CSF sTREM2, and by exploring the potential modifying role of these variants on the well-established associations between CSF sTREM2 as well as TREM2 transcript levels in the brain with AD neuropathology. Biomarker analyses leveraged data from the Vanderbilt Memory & Aging Project (n = 127, age = 72 ± 6.43) and were replicated in the Alzheimer’s Disease Neuroimaging Initiative (n = 399, age = 73 ± 7.39). Autopsy analyses were performed leveraging data from the Religious Orders Study and Rush Memory and Aging Project (n= 577, age = 89 ± 6.46). We found that the protective variant rs1582763 attenuated the association between CSF sTREM2 and Aβ 40 (β= -0.44, p-value= 0.017) and replicated this interaction in ADNI (β = -0.27, p = 0.017). We did not observe this same interaction effect between TREM2 mRNA levels and Aβ peptides in brain (Aβ total β = -0.14, p = 0.629; Aβ 1-38 , β = 0.11, p = 0.200). In contrast to the effects on Aβ, the minor allele of this same variant seemed to enhance the association with blood–brain barrier dysfunction (β = 7.0e-4, p = 0.009), suggesting that elevated sTREM2 may carry a much different interpretation in carriers vs. non-carriers of this allele. When evaluating the risk variant (rs6591561) across datasets, we did not observe a statistically significant interaction against any outcome in VMAP and observed opposing directions of associations in ADNI and ROS/MAP on Aβ levels. Together, our results suggest that the protective effect of rs1582763 may act by decoupling the associations between sTREM2 and amyloid abundance, providing important mechanistic insight into sTREM2 changes and highlighting the need to incorporate genetic context into the analysis of sTREM2 levels, particularly if leveraged as a clinical biomarker of disease in the future.

59 BASIC BIOLOGICAL SCIENCES↗