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At least 253 records · Page 14

Update on NASA’s ISRU Development and Mission Plans for the Artemis Program

In 2017, NASA initiated the Artemis program to send astronauts back to the lunar surface, create a sustainable human lunar exploration program, and lead the first human exploration mission to the Mars surface. While much of NASA’s plans for the Artemis program currently focus on the Human Lunar Return and the ability for astronauts to explore the lunar surface for limited durations each year, the longer-term vision for the Artemis program is to enable sustained human exploration and commercial operations in cis-lunar space and the lunar surface. An important aspect of achieving this long-term vision, is to better understand and characterize the resources on the Moon and Mars and learn how to extract and use these resources. Known as In Situ Resource Utilization (ISRU), the identification, mapping, extraction, and processing of space resources has the potential to greatly reduce the cost and risk of human exploration. These are achieved by reducing what needs to be delivered from Earth and the dependency on these supplies, lowering costs through commercial operations, and expanding infrastructure for safer and more capable exploration and surface operations. To guide development of ISRU technologies and systems on the ground and demonstrate these capabilities on the Moon and Mars, the NASA Space Technology Mission Directorate (STMD) created and released the ISRU Envisioned Future Priorities (EFP) strategic plan in 2022 and updated it in 2023. While lunar ISRU technology development had already started, these publicly released strategic plans have been used to guide and prioritize technology development, and assess the progress in achieving the vision. Since the release of the ISRU EFP, there have been several significant activities/events that have occurred with respect to human lunar exploration, surface infrastructure, and ISRU. One was the release of the Artemis Architecture Definition Document Revision 1 that included ISRU as a sub-architecture. The second was the release of several STMD solicitations including the Announcement of Collaborative Opportunities (ACO) and Tipping Point (TP). The third was the release of a Request for Information for the Lunar Infrastructure Foundational Technology-1 (LIFT-1) mission with the primary objective of extracting oxygen from lunar regolith. The fourth was the release of STMD technology and capability Shortfalls, and the review, ranking by numerous stakeholders and individuals, and subsequent prioritization of the Shortfalls that will be utilized in future solicitation and development plans. This paper will provide an overview and status of on-going technology and system development activities, an update of ISRU into the Artemis campaign, an update on ISRU-related mission, and the impacts of the Shortfall prioritization.

NASA↗

Moon to Mars In Situ Resource Utilization (ISRU) Status Update

In 2017, NASA initiated the Artemis program to send astronauts back to the lunar surface, create a sustainable human lunar exploration program, and lead the first human exploration mission to the Mars surface. While much of NASA’s plans for the Artemis program currently focus on the Human Lunar Return and the ability for astronauts to explore the lunar surface for limited durations each year, the longer-term vision for the Artemis program is to enable sustained human exploration and commercial operations in cis-lunar space and the lunar surface. An important aspect of achieving this long-term vision, is to better understand and characterize the resources on the Moon and Mars and learn how to extract and use these resources. Known as In Situ Resource Utilization (ISRU), the identification, mapping, extraction, and processing of space resources has the potential to greatly reduce the cost and risk of human exploration. These are achieved by reducing what needs to be delivered from Earth and the dependency on these supplies, lowering costs through commercial operations, and expanding infrastructure for safer and more capable exploration and surface operations. To guide development of ISRU technologies and systems on the ground and demonstrate these capabilities on the Moon and Mars, the NASA Space Technology Mission Directorate (STMD) created and released the ISRU Envisioned Future Priorities (EFP) strategic plan in 2022 and updated it in 2023. While lunar ISRU technology development had already started, these publicly released strategic plans have been used to guide and prioritize technology development, and assess the progress in achieving the vision. Since the release of the ISRU EFP, there have been several significant activities/events that have occurred with respect to human lunar exploration, surface infrastructure, and ISRU. This presentation will provide an overview and status of on-going technology and system development activities, an update of ISRU into the Artemis campaign, an update on ISRU-related activities.

NASA↗

Leveraging Terrestrial Industry for Utilization of Space Resources

NASA's Journey to Mars: Pioneering Next Steps in Space Exploration released in October of 2015 states that NASA is working toward the capability to work, operate, and sustainably live safely beyond Earth. To progress from our current "Earth-Reliant" approach to exploration and eventually become "Earth Independent", we need to first identify resources in space and then learn to use and harvest them to minimize logistics from Earth, reduce costs, and enable sustainable and affordable space transportation and surface operations. Known as In Situ Resource Utilization (ISRU), the collection and conversion of space resources into products such as propellants, fuel cell reactants, and life support consumables can greatly reduce the mass, cost, and risk of space exploration. Also, the ability to perform civil engineering, construction, and manufacturing at sites of exploration can also allow for increased crew safety and sustainable growth in critical infrastructure. Much of what NASA wants to do on the Moon and Mars with respect to harnessing and utilizing space resources has been performed and perfected on Earth over the centuries. While minimizing mass and operating in the vacuum of space may be unique challenges to NASA, both terrestrial industry and NASA face many of the same challenges associated with operating in severe environments, minimizing maintenance and logistics, maximizing performance per unit mass and volume, performing remote and autonomous operations, and integrating hardware from many vendors and countries. In the end, both NASA and terrestrial industry need to obtain a return on the investment for the development and deployment of these capabilities. This paper will first examine what is ISRU and what are the space resources of interest. The paper will than discuss what are NASA's approach, life cycle, and economic considerations for implementing ISRU. The paper will outline the site and infrastructure needs associated with a phased implementation of ISRU into human missions to the Moon and Mars. The paper will than assess what technologies and operations from terrestrial industries are relevant and synergistic with ISRU (from prospecting to product storage), and what challenges and similarities between the two can be exploited. Lastly, the paper will end with a discussion on where do we go from here for industry and NASA to collaborate.

Sanders, Gerald B.↗

NASA Crew Health & Performance Capability Development for Exploration: 2021 to 2022 Overview

Radiation, reduced gravity, distance from earth, isolation and confinement, and habitation within artificially created and controlled life support environments are hazards that present risk to human space explorers. In many cases, research is required to characterize those risks and help identify risk mitigation strategies. Where new capabilities are necessary to maintain crew health and performance (CHP) during exploration missions, a multi-step process is followed: 1) a Capability Gap is defined; 2) a plan or “roadmap” to develop that capability is established based on agency priorities and anticipated mission development timelines; and 3) work defined on the roadmap is then initiated as resources allow, with the objective that the capability will be available in time to support the future mission. Over the past year, significant progress has occurred in CHP technology development, ground testbed development, ground-based testing, and in preparations for ISS technology demonstrations. This paper provides a development update in the following capability areas: crew health countermeasures, EVA physiology and performance, food and nutrition, exploration medical capabilities, and radiation. Project overviews will include descriptions of CHP development activities over the past year, the human system risks and capability gaps being targeted, as well as planned follow-on activities and anticipated program infusion points.

Andrew F J Abercromby↗

Enabling Renewable Energy While Protecting Wildlife: An Ecological Risk-Based Approach to Wind Energy Development Using Ecosystem-Based Management Values

Acceptance of wind energy development is challenged by stakeholders’ concerns about potential effects on the environment, specifically on wildlife, such as birds, bats, and (for offshore wind) marine animals, and the habitats that support them. Communities near wind energy developments are also concerned with social and economic impacts, as well as impacts on aesthetics, historical sites, and recreation and tourism. Lack of a systematic, widely accepted, and balanced approach for measuring the potential damage to wildlife, habitats, and communities continues to leave wind developers, regulators, and other stakeholders in an uncertain position. This paper explores ecological risk-based management (RBM) in wind energy development for land-based and offshore wind installations. This paper provides a framework for the adaptation of ecosystem-based management to wind energy development and examines that framework through a series of case studies and best management practices for applying risk-based principles to wind energy. Ten case studies indicate that wind farm monitoring is often driven by regulatory requirements that may not be underpinned by scientific questions. While each case applies principles of adaptive management, there is room for improvement in applying scientific principles to the data collection and analysis. Challenges and constraints for wind farm development to meet RBM framework criteria include collecting sufficient baseline and monitoring data year-round, engaging stakeholder facilitators, and bringing together large and diverse scientific teams. The RBM framework approach may provide insights for improved siting and consenting/permitting processes for regulators and their advisors, particularly in those nations where wind energy is still in the early development stages on land or at sea.

17 WIND ENERGY↗

Methods for the Enhancement of Security Probabilistic Risk Assessments

The US Department of Energy is exploring the methods associated with probabilistic risk assessment (PRA) and how they could be used to enhance physical security evaluations for nuclear facilities. A brief review of both international and US Nuclear Regulatory Commission physical security assessment methods is presented. From this review, and with an understanding of the technical elements associated with a traditional nuclear safety PRA, several observations are made pertaining to where physical security analysis methods could be enhanced. These observations principally support and enhance the answers within a physical security context to the risk triplet: (1) What can go wrong? (2) What is the likelihood? and (3) What are the consequences? Finally, benefits and technical challenges toward the development of a full security PRA are presented.

45 MILITARY TECHNOLOGY, WEAPONRY, AND NATIONAL DEF↗

Aeronautics and Space Report of the President: Fiscal Year 2009 Activities

In fiscal year 2009 (FY 09), the Exploration Systems Mission Directorate's (ESMD) Advanced Capabilities Division (ACD) provided critical research and technology products that reduced operational and technical risks for the flight systems being developed by the Constellation Program.1 These products addressed high-priority technology requirements for lunar exploration; risk mitigation related to astronaut health and performance; basic research in life and physical sciences using the International Space Station (ISS), free-flying spacecraft, and ground-based laboratories; and lunar robotic missions to gather data relevant to future human lunar missions.

Source record↗

Flexible-Path Human Exploration

In the fourth quarter of 2009 an in-house, multi-center NASA study team briefly examined "Flexible Path" concepts to begin understanding characteristics, content, and roles of potential missions consistent with the strategy proposed by the Augustine Committee. We present an overview of the study findings. Three illustrative human/robotic mission concepts not requiring planet surface operations are described: assembly of very large in-space telescopes in cis-lunar space; exploration of near Earth objects (NEOs); exploration of Mars' moon Phobos. For each, a representative mission is described, technology and science objectives are outlined, and a basic mission operations concept is quantified. A fourth type of mission, using the lunar surface as preparation for Mars, is also described. Each mission's "capability legacy" is summarized. All four illustrative missions could achieve NASA's stated human space exploration objectives and advance human space flight toward Mars surface exploration. Telescope assembly missions would require the fewest new system developments. NEO missions would offer a wide range of deep-space trip times between several months and two years. Phobos exploration would retire several Marsclass risks, leaving another large remainder set (associated with entry, descent, surface operations, and ascent) for retirement by subsequent missions. And extended lunar surface operations would build confidence for Mars surface missions by addressing a complementary set of risks. Six enabling developments (robotic precursors, ISS exploration testbed, heavy-lift launch, deep-space-capable crew capsule, deep-space habitat, and reusable in-space propulsion stage) would apply across multiple program sequence options, and thus could be started even without committing to a specific mission sequence now. Flexible Path appears to be a viable strategy, with meaningful and worthy mission content.

Augustine↗

Crew Health and Performance Integrated Data Architecture (CHP-IDA) Project

BACKGROUND: Future Human Exploration missions introduce a new paradigm as crews move further from the resupply and near real-time ground support typical of Low Earth Orbit missions today. Without immediate support from ground-based personnel, exploration crews will be more reliant on inflight data and technology to respond to emergencies and anomalies. A data architecture to support a new generation of technologies, employing advanced analytical and predictive modeling techniques, is needed to enable crew autonomy. OVERVIEW: The Crew Health and Performance Integrated Data Architecture (CHP-IDA) project funded by NASA’s Exploration Medical Integrated Product Team (XMIPT) is laying a foundation for future in-flight informatics by providing a back-end architecture for collecting, storing, and integrating multiple sources of data generated by and around the crew. CHP-IDA provides a platform for common data models and Application Programming Interfaces to access, integrate, process, and display CHP data (e.g., environmental, exercise, medical, sleep, performance, etc.). This will facilitate the increased situation awareness and decision support required by the crew and remote support of exploration missions. This presentation will describe the currently ongoing effort to develop and evaluate a path-to-flight concept of the CHP-IDA software and its core capabilities. Current integrations will be discussed, including analytics for Extravehicular Activity metabolic rate and data ingestion from a multi-functional integrated medical device. The presentation will also provide examples of scenarios used to demonstrate the CHP-IDA through human-in-the-loop test bed activities as well as examples of appropriate system performance metrics. DISCUSSION: Today, in-flight data is often siloed, unsynchronized, and largely inaccessible in real time. Many data sets require manual entry and/or data transfer between vehicles and the ground. These issues contribute to risks in supporting exploration medical capabilities. The CHP-IDA is a back-end data system providing core capabilities needed for timely and meaningful data insights across CHP domains to crew and remote personnel to enable increased crew autonomy. Future work includes collaboration with additional CHP domains, new technology integrations, and further demonstrations of the IDA within different vehicle and communication latency contexts. LEARNING OBJECTIVES 1. The audience will understand that the CHP-IDA is a back-end system, providing a platform to facilitate access, promote decision tools, and provide meaningful insights to crew and to remote stakeholders during exploration missions. 2. The audience will gain insight into human-centered research and activities used to discover CHP domain data needs and pain points and how this information is used to guide development of the IDA.

Exploration↗

Cancer Risk Map for the Surface of Mars

We discuss calculations of the median and 95th percentile cancer risks on the surface of Mars for different solar conditions. The NASA Space Radiation Cancer Risk 2010 model is used to estimate gender and age specific cancer incidence and mortality risks for astronauts exploring Mars. Organ specific fluence spectra and doses for large solar particle events (SPE) and galactic cosmic rays (GCR) at various levels of solar activity are simulated using the HZETRN/QMSFRG computer code, and the 2010 version of the Badhwar and O Neill GCR model. The NASA JSC propensity model of SPE fluence and occurrence is used to consider upper bounds on SPE fluence for increasing mission lengths. In the transport of particles through the Mars atmosphere, a vertical distribution of Mars atmospheric thickness is calculated from the temperature and pressure data of Mars Global Surveyor, and the directional cosine distribution is implemented to describe the spherically distributed atmospheric distance along the slant path at each elevation on Mars. The resultant directional shielding by Mars atmosphere at each elevation is coupled with vehicle and body shielding for organ dose estimates. Astronaut cancer risks are mapped on the global topography of Mars, which was measured by the Mars Orbiter Laser Altimeter. Variation of cancer risk on the surface of Mars is due to a 16-km elevation range, and the large difference is obtained between the Tharsis Montes (Ascraeus, Pavonis, and Arsia) and the Hellas impact basin. Cancer incidence risks are found to be about 2-fold higher than mortality risks with a disproportionate increase in skin and thyroid cancers for all astronauts and breast cancer risk for female astronauts. The number of safe days on Mars to be below radiation limits at the 95th percent confidence level is reported for several Mission design scenarios.

Kim, Myung-Hee Y.↗

Quantitative modeling of carcinogenesis induced by single beams or mixtures of space radiations using targeted and non-targeted effects

Abstract Ionizing radiations encountered by astronauts on deep space missions produce biological damage by two main mechanisms: (1) Targeted effects (TE) due to direct traversals of cells by ionizing tracks. (2) Non-targeted effects (NTE) caused by release of signals from directly hit cells. The combination of these mechanisms generates non-linear dose response shapes, which need to be modeled quantitatively to predict health risks from space exploration. Here we used a TE + NTE model to analyze data on APC (1638N/+) mouse tumorigenesis induced by space-relevant doses of protons, 4 He, 12 C, 16 O, 28 Si or 56 Fe ions, or γ rays. A customized weighted Negative Binomial distribution was used to describe the radiation type- and dose-dependent data variability. This approach allowed detailed quantification of dose–response shapes, NTE- and TE-related model parameters, and radiation quality metrics (relative biological effectiveness, RBE, and radiation effects ratio, RER, relative to γ rays) for each radiation type. Based on the modeled responses for each radiation type, we predicted the tumor yield for a Mars-mission-relevant mixture of these radiations, using the recently-developed incremental effect additivity (IEA) synergy theory. The proposed modeling approach can enhance current knowledge about quantification of space radiation quality effects, dose response shapes, and ultimately the health risks for astronauts.

60 APPLIED LIFE SCIENCES↗

INGENIOUS - Great Basin Regional Dataset Compilation

This is the regional dataset compilation for the INnovative Geothermal Exploration through Novel Investigations Of Undiscovered Systems (INGENIOUS) project. The primary goal of this project is to accelerate discoveries of new, commercially viable hidden geothermal systems while reducing the exploration and development risks for all geothermal resources. These datasets will be used in INGENIOUS as input features for predicting geothermal favorability throughout the Great Basin study area. Datasets consist of shapefiles, geotiffs, tabular spreadsheets, and metadata that describe: 2-meter temperature probe surveys, quaternary faults and volcanic features, geodetic shear and dilation models, heat flow, magnetotellurics (conductance), magnetics, gravity, paleogeothermal features (such as sinter and tufa deposits), seismicity, spring and well temperatures, spring and well aqueous geochemistry analyses, thermal conductivity, and fault slip and dilation tendency. For additional project information, see the INGENIOUS project site linked in the submission. Terms of use: These datasets are provided "as is", and the contributors assume no responsibility for any errors or omissions. The user assumes the entire risk associated with their use of these data and bears all responsibility in determining whether these data are fit for their intended use. These datasets may be redistributed with attribution (see citation information below). Please refer to the license information on this page for full licensing terms and conditions.

15 GEOTHERMAL ENERGY↗

Exploration Laboratory Analysis - ARC

The Exploration Laboratory Analysis (ELA) project supports the Exploration Medical Capability (ExMC) risk, Risk of Inability to Adequately Treat an Ill or Injured Crew Member, and ExMC Gap 4.05: Lack of minimally invasive in-flight laboratory capabilities with limited consumables required for diagnosing identified Exploration Medical Conditions. To mitigate this risk, the availability of inflight laboratory analysis instrumentation has been identified as an essential capability in future exploration missions. Mission architecture poses constraints on equipment and procedures that will be available to treat evidence-based medical conditions according to the Space Medicine Exploration Medical Conditions List (SMEMCL). The SMEMCL provided diagnosis and treatment for the evidence-based medical conditions and hence, a basis for developing ELA functional requirements.

Krihak, Michael K.↗

Exploration Laboratory Analysis FY13

The Exploration Laboratory Analysis (ELA) project supports the Exploration Medical Capability (ExMC) risk, which is stated as the Risk of Inability to Adequately Treat an Ill or Injured Crew Member, and ExMC Gap 4.05: Lack of minimally invasive in-flight laboratory capabilities with limited consumables required for diagnosing identified Exploration Medical Conditions. To mitigate this risk, the availability of inflight laboratory analysis instrumentation has been identified as an essential capability in future exploration missions. Mission architecture poses constraints on equipment and procedures that will be available to treat evidence-based medical conditions according to the Space Medicine Exploration Medical Conditions List (SMEMCL), and to perform human research studies on the International Space Station (ISS) that are supported by the Human Health and Countermeasures (HHC) element. Since there are significant similarities in the research and medical operational requirements, ELA hardware development has emerged as a joint effort between ExMC and HHC. In 2012, four significant accomplishments were achieved towards the development of exploration laboratory analysis for medical diagnostics. These achievements included (i) the development of high priority analytes for research and medical operations, (ii) the development of Level 1 functional requirements and concept of operations documentation, (iii) the selection and head-to-head competition of in-flight laboratory analysis instrumentation, and (iv) the phase one completion of the Small Business Innovation Research (SBIR) projects under the topic Smart Phone Driven Blood-Based Diagnostics. To utilize resources efficiently, the associated documentation and advanced technologies were integrated into a single ELA plan that encompasses ExMC and HHC development efforts. The requirements and high priority analytes was used in the selection of the four in-flight laboratory analysis performers. Based upon the competition results, a down select process will be performed in the upcoming year. Looking ahead, this unified effort has positioned each element for an in-flight lab analysis demonstration of select diagnostics measurements in the 2015 timeframe.

Krihak, Michael↗

Exploration Medical Capability Science and Research Overview and Update

The mission of the Exploration Medical Capability (ExMC) Element is to advance medical system design and risk-informed decision making for exploration beyond Low Earth Orbit to promote human health and performance in space. To accomplish this mission, ExMC focuses on several key areas: • Investigating specific risks that are relevant for human exploration spaceflight, including in-flight medical conditions, degraded or toxic medications, and renal stones • Developing medical probabilistic risk analysis tools that are integrated with systems engineering processes to inform the medical system trade space and support the development of robust requirements • Demonstrating and defining requirements for a prototype clinical decision support system • Developing and demonstrating novel medical technologies that will improve future medical capabilities in space This presentation will focus on selected scientific and technical conceptual drivers for the Element and its current and future research risks and gaps while providing an overview of the Element’s progress in 2021 and areas of focus for 2022.

Benjamin Easter↗

Automation of Solid Oxyde Electrolyzer Cell (SOEC) & Stack Assembly

The work performed under this agreement before the No/Go decision amounted to the following: 1. Preliminary manufacturing requirements defined by business sensitivity, baseline processes & risk assessment; 2. Process & materials development, in-line gauge exploration, and preliminary automation work used to reduce risk & further refine equipment specifications; 3. “Request for Quote” issued to multiple suppliers for major equipment; 4. Application specific equipment, hardware, and fixturing will be more beneficial to fabricate inhouse; 5.Current proposals & estimates meet cycle time, capital spend, & direct labor; space is on target but requires awareness; 6. Team will continue to explore opportunities to reduce risk (dry time, traceability); 7. Go / No-Go, Purchase Orders, Equipment build & commissioning next All other future task were not completed because during the Go /No-Go decision it was confirmed this project was a "No-Go" and did not proceed past BP1; these included the following: 1. Preliminary manufacturing requirements defined by business sensitivity, baseline processes & risk assessment; 2. Process & materials development, in-line gauge exploration, and preliminary automation work used to reduce risk & further refine equipment specifications; 3. “Request for Quote” issued to multiple suppliers for major equipment; 4. Application specific equipment, hardware, and fixturing will be more beneficial to fabricate inhouse; 5. Current proposals & estimates meet cycle time, capital spend, & direct labor; space is on target but requires awareness; 6. Team will continue to explore opportunities to reduce risk (dry time, traceability) In final preparation of the termination of the Automation of Solid Oxyde Electrolyzer Cell (SOEC) & Stack Assembly, Cummins has purchased no equipment with government funds, and there is no government-owned property in Cummins possession related to this project. Minimal labor and travel were completed and paid. This acts as the Final technical report and concludes our business with DOE on this grant.

36 MATERIALS SCIENCE↗

Metagenomic Methods for Addressing NASA's Planetary Protection Policy Requirements on Future Missions: A Workshop Report

Molecular biology methods and technologies have advanced substantially over the past decade. These new molecular methods should be incorporated among the standard tools of planetary protection (PP) and could be validated for incorporation by 2026. To address the feasibility of applying modern molecular techniques to such an application, NASA conducted a technology workshop with private industry partners, academics, and government agency stakeholders, along with NASA staff and contractors. The technical discussions and presentations of the Multi-Mission Metagenomics Technology Development Workshop focused on modernizing and supplementing the current PP assays. The goals of the workshop were to assess the state of metagenomics and other advanced molecular techniques in the context of providing a validated framework to supplement the bacterial endospore-based NASA Standard Assay and to identify knowledge and technology gaps. In particular, workshop participants were tasked with discussing metagenomics as a stand-alone technology to provide rapid and comprehensive analysis of total nucleic acids and viable microorganisms on spacecraft surfaces, thereby allowing for the development of tailored and cost-effective microbial reduction plans for each hardware item on a spacecraft. Workshop participants recommended metagenomics approaches as the only data source that can adequately feed into quantitative microbial risk assessment models for evaluating the risk of forward (exploring extraterrestrial planet) and back (Earth harmful biological) contamination. Participants were unanimous that a metagenomics workflow, in tandem with rapid targeted quantitative (digital) PCR, represents a revolutionary advance over existing methods for the assessment of microbial bioburden on spacecraft surfaces. The workshop highlighted low biomass sampling, reagent contamination, and inconsistent bioinformatics data analysis as key areas for technology development. Finally, it was concluded that implementing metagenomics as an additional workflow for addressing concerns of NASA's robotic mission will represent a dramatic improvement in technology advancement for PP and will benefit future missions where mission success is affected by backward and forward contamination.

59 BASIC BIOLOGICAL SCIENCES↗

BIN1 protein isoforms are differentially expressed in astrocytes, neurons, and microglia: neuronal and astrocyte BIN1 are implicated in tau pathology

Background: Identified as an Alzheimer’s disease (AD) susceptibility gene by genome wide-association studies, BIN1 has 10 isoforms that are expressed in the Central Nervous System (CNS). The distribution of these isoforms in different cell types, as well as their role in AD pathology still remains unclear. Methods: Utilizing antibodies targeting specific BIN1 epitopes in human post-mortem tissue and analyzing mRNA expression data from purified microglia, we identified three isoforms expressed in neurons and astrocytes (isoforms 1, 2 and 3) and four isoforms expressed in microglia (isoforms 6, 9, 10 and 12). The abundance of selected peptides, which correspond to groups of BIN1 protein isoforms, was measured in dorsolateral prefrontal cortex, and their relation to neuropathological features of AD was assessed. Results: Peptides contained in exon 7 of BIN1’s N-BAR domain were found to be significantly associated with ADrelated traits and, particularly, tau tangles. Decreased expression of BIN1 isoforms containing exon 7 is associated with greater accumulation of tangles and subsequent cognitive decline, with astrocytic rather than neuronal BIN1 being the more likely culprit. These effects are independent of the BIN1 AD risk variant. Conclusions: Exploring the molecular mechanisms of specific BIN1 isoforms expressed by astrocytes may open new avenues for modulating the accumulation of Tau pathology in AD. Keywords: BIN1 isoforms, Alzheimer’s disease, Amyloid, Tau, Microglia, Astrocytes, Neurons

Taga, Mariko↗