Trial of Prasinezumab in Early-Stage Parkinson's Disease.

BACKGROUND: Aggregated α-synuclein plays an important role in the pathogenesis of Parkinson's disease. The monoclonal antibody prasinezumab, directed at aggregated α-synuclein, is being studied for its effect on Parkinson's disease. METHODS: In this phase 2 trial, we randomly assigned participants with early-stage Parkinson's disease in a 1:1:1 ratio to receive intravenous placebo or prasinezumab at a dose of 1500 mg or 4500 mg every 4 weeks for 52 weeks. The primary end point was the change from baseline to week 52 in the sum of scores on parts I, II, and III of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 236, with higher scores indicating greater impairment). Secondary end points included the dopamine transporter levels in the putamen of the hemisphere ipsilateral to the clinically more affected side of the body, as measured by 123I-ioflupane single-photon-emission computed tomography (SPECT). RESULTS: A total of 316 participants were enrolled; 105 were assigned to receive placebo, 105 to receive 1500 mg of prasinezumab, and 106 to receive 4500 mg of prasinezumab. The baseline mean MDS-UPDRS scores were 32.0 in the placebo group, 31.5 in the 1500-mg group, and 30.8 in the 4500-mg group, and mean (±SE) changes from baseline to 52 weeks were 9.4±1.2 in the placebo group, 7.4±1.2 in the 1500-mg group (difference vs. placebo, -2.0; 80% confidence interval [CI], -4.2 to 0.2; P = 0.24), and 8.8±1.2 in the 4500-mg group (difference vs. placebo, -0.6; 80% CI, -2.8 to 1.6; P = 0.72). There was no substantial difference between the active-treatment groups and the placebo group in dopamine transporter levels on SPECT. The results for most clinical secondary end points were similar in the active-treatment groups and the placebo group. Serious adverse events occurred in 6.7% of the participants in the 1500-mg group and in 7.5% of those in the 4500-mg group; infusion reactions occurred in 19.0% and 34.0%, respectively. CONCLUSIONS: Prasinezumab therapy had no meaningful effect on global or imaging measures of Parkinson's disease progression as compared with placebo and was associated with infusion reactions. (Funded by F. Hoffmann-La Roche and Prothena Biosciences; PASADENA ClinicalTrials.gov number, NCT03100149.).

Dynamic local mRNA localization and translation occurs during the postnatal molecular maturation of perivascular astrocytic processes.

Astrocytes are highly ramified and send out perivascular processes (PvAPs) that entirely sheathe the brain's blood vessels. PvAPs are equipped with an enriched molecular repertoire that sustains astrocytic regulatory functions at the vascular interface. In the mouse, PvAP development starts after birth and is essentially complete by postnatal day (P) 15. Progressive molecular maturation also occurs over this period, with the acquisition of proteins enriched in PvAPs. The mechanisms controlling the development and molecular maturation of PvAPs have not been extensively characterized. We reported previously that mRNAs are distributed unequally in mature PvAPs and are locally translated. Since dynamic mRNA localization and local translation influence the cell's polarity, we hypothesized that they might sustain the postnatal maturation of PvAPs. Here, we used a combination of molecular biology and imaging approaches to demonstrate that the development of PvAPs is accompanied by the transport of mRNA and polysomal mRNA into PvAPs, the development of a rough endoplasmic reticulum (RER) network and Golgi cisternae, and local translation. By focusing on genes and proteins that are selectively or specifically expressed in astrocytes, we characterized the developmental profile of mRNAs, polysomal mRNAs and proteins in PvAPs from P5 to P60. We found that some polysomal mRNAs polarized progressively towards the PvAPs. Lastly, we found that expression and localization of mRNAs in developing PvAPs is perturbed in a mouse model of megalencephalic leukoencephalopathy with subcortical cysts. Our results indicate that dynamic mRNA localization and local translation influence the postnatal maturation of PvAPs.

PAI-1 production by reactive astrocytes drives tissue dysfibrinolysis in multiple sclerosis models.

BACKGROUND: In multiple sclerosis (MS), disturbance of the plasminogen activation system (PAS) and blood brain barrier (BBB) disruption are physiopathological processes that might lead to an abnormal fibrin(ogen) extravasation into the parenchyma. Fibrin(ogen) deposits, usually degraded by the PAS, promote an autoimmune response and subsequent demyelination. However, the PAS disruption is not well understood and not fully characterized in this disorder. METHODS: Here, we characterized the expression of PAS actors during different stages of two mouse models of MS (experimental autoimmune encephalomyelitis-EAE), in the central nervous system (CNS) by quantitative RT-PCR, immunohistofluorescence and fluorescent in situ hybridization (FISH). Thanks to constitutive PAI-1 knockout mice (PAI-1 KO) and an immunotherapy using a blocking PAI-1 antibody, we evaluated the role of PAI-1 in EAE models and its impact on physiopathological processes such as fibrin(ogen) deposits, lymphocyte infiltration and demyelination. RESULTS: We report a striking overexpression of PAI-1 in reactive astrocytes during symptomatic phases, in two EAE mouse models of MS. This increase is concomitant with lymphocyte infiltration and fibrin(ogen) deposits in CNS parenchyma. By genetic invalidation of PAI-1 in mice and immunotherapy using a blocking PAI-1 antibody, we demonstrate that abolition of PAI-1 reduces the severity of EAE and occurrence of relapses in two EAE models. These benefits are correlated with a decrease in fibrin(ogen) deposits, infiltration of T4 lymphocytes, reactive astrogliosis, demyelination and axonal damage. CONCLUSION: These results demonstrate that a deleterious overexpression of PAI-1 by reactive astrocytes leads to intra-parenchymal dysfibrinolysis in MS models and anti-PAI-1 strategies could be a new therapeutic perspective for MS.

AstroDot - a new method for studying the spatial distribution of mRNA in astrocytes.

Astrocytes are morphologically complex and use local translation to regulate distal functions. To study the distribution of mRNA in astrocytes, we combined mRNA detection via in situ hybridization with immunostaining of the astrocyte-specific intermediate filament glial fibrillary acidic protein (GFAP). mRNAs at the level of GFAP-immunolabelled astrocyte somata, and large and fine processes were analysed using AstroDot, an ImageJ plug-in and the R package AstroStat. Taking the characterization of mRNAs encoding GFAP-α and GFAP-δ isoforms as a proof of concept, we showed that they mainly localized on GFAP processes. In the APPswe/PS1dE9 mouse model of Alzheimer's disease, the density and distribution of both α and δ forms of Gfap mRNA changed as a function of the region of the hippocampus and the astrocyte's proximity to amyloid plaques. To validate our method, we confirmed that the ubiquitous Rpl4 (large subunit ribosomal protein 4) mRNA was present in astrocyte processes as well as in microglia processes immunolabelled for ionized calcium binding adaptor molecule 1 (Iba1; also known as IAF1). In summary, this novel set of tools allows the characterization of mRNA distribution in astrocytes and microglia in physiological or pathological settings.

Astrocytes in the regulation of cerebrovascular functions.

Astrocytes are the most numerous type of neuroglia in the brain and have a predominant influence on the cerebrovascular system; they control perivascular homeostasis, the integrity of the blood-brain barrier, the dialogue with the peripheral immune system, the transfer of metabolites from the blood, and blood vessel contractility in response to neuronal activity. These regulatory processes occur in a specialized interface composed of perivascular astrocyte extensions that almost completely cover the cerebral blood vessels. Scientists have only recently started to study how this interface is formed and how it influences cerebrovascular functions. Here, we review the literature on the astrocytes' role in the regulation of the cerebrovascular system. We cover the anatomy and development of the gliovascular interface, the known gliovascular functions, and molecular factors, the latter's implication in certain pathophysiological situations, and recent cutting-edge experimental tools developed to examine the astrocytes' role at the vascular interface. Finally, we highlight some open questions in this field of research.

Dp71 contribution to the molecular scaffold anchoring aquaporine-4 channels in brain macroglial cells.

Intellectual disability in Duchenne muscular dystrophy has been associated with the loss of dystrophin-protein 71, Dp71, the main dystrophin-gene product in the adult brain. Dp71 shows major expression in perivascular macroglial endfeet, suggesting that dysfunctional glial mechanisms contribute to cognitive impairments. In the present study, we investigated the molecular alterations induced by a selective loss of Dp71 in mice, using semi-quantitative immunogold analyses in electron microscopy and immunofluorescence confocal analyses in brain sections and purified gliovascular units. In macroglial pericapillary endfeet of the cerebellum and hippocampus, we found a drastic reduction (70%) of the polarized distribution of aquaporin-4 (AQP4) channels, a 50% reduction of ß-dystroglycan, and a complete loss of α1-syntrophin. Interestingly, in the hippocampus and cortex, these effects were not homogeneous: AQP4 and AQP4ex isoforms were mostly lost around capillaries but preserved in large vessels corresponding to pial arteries, penetrating cortical arterioles, and arterioles of the hippocampal fissure, indicating the presence of Dp71-independent pools of AQP4 in these vascular structures. In conclusion, the depletion of Dp71 strongly alters the distribution of AQP4 selectively in macroglial perivascular endfeet surrounding capillaries. This effect likely affects water homeostasis and blood-brain barrier functions and may thus contribute to the synaptic and cognitive defects associated with Dp71 deficiency.

Defining freshwater as a natural resource: A framework linking water use to the area of protection natural resources.

PURPOSE: While many examples have shown unsustainable use of freshwater resources, existing LCIA methods for water use do not comprehensively address impacts to natural resources for future generations. This framework aims to (1) define freshwater resource as an item to protect within the Area of Protection (AoP) natural resources, (2) identify relevant impact pathways affecting freshwater resources, and (3) outline methodological choices for impact characterization model development. METHOD: Considering the current scope of the AoP natural resources, the complex nature of freshwater resources and its important dimensions to safeguard safe future supply, a definition of freshwater resource is proposed, including water quality aspects. In order to clearly define what is to be protected, the freshwater resource is put in perspective through the lens of the three main safeguard subjects defined by Dewulf et al. (2015). In addition, an extensive literature review identifies a wide range of possible impact pathways to freshwater resources, establishing the link between different inventory elementary flows (water consumption, emissions and land use) and their potential to cause long-term freshwater depletion or degradation. RESULTS AND DISCUSSION: Freshwater as a resource has a particular status in LCA resource assessment. First, it exists in the form of three types of resources: flow, fund, or stock. Then, in addition to being a resource for human economic activities (e.g. hydropower), it is above all a non-substitutable support for life that can be affected by both consumption (source function) and pollution (sink function). Therefore, both types of elementary flows (water consumption and emissions) should be linked to a damage indicator for freshwater as a resource. Land use is also identified as a potential stressor to freshwater resources by altering runoff, infiltration and erosion processes as well as evapotranspiration. It is suggested to use the concept of recovery period to operationalize this framework: when the recovery period lasts longer than a given period of time, impacts are considered to be irreversible and fall into the concern of freshwater resources protection (i.e. affecting future generations), while short-term impacts effect the AoP ecosystem quality and human health directly. It is shown that it is relevant to include this concept in the impact assessment stage in order to discriminate the long-term from the short-term impacts, as some dynamic fate models already do. CONCLUSION: This framework provides a solid basis for the consistent development of future LCIA methods for freshwater resources, thereby capturing the potential long-term impacts that could warn decision makers about potential safe water supply issues in the future.

A Multimedia Hydrological Fate Modeling Framework To Assess Water Consumption Impacts in Life Cycle Assessment.

Many new methods have recently been developed to address environmental consequences of water consumption in life cycle assessment (LCA). However, such methods can only partially be compared and combined, because their modeling structure and metrics are inconsistent. Moreover, they focus on specific water sources (e.g., river) and miss description of transport flows between water compartments (e.g., from river to atmosphere via evaporation) and regions (e.g., atmospheric advection). Consequently, they provide a partial regard of the local and global hydrological cycle and derived impacts on the environment. This paper proposes consensus-based guidelines for a harmonized development of the next generation of water consumption LCA indicators, with a focus on consequences of water consumption on ecosystem quality. To include the consideration of the multimedia water fate between compartments of the water cycle, we provide spatial regionalization and temporal specification guidance. The principles and recommendations of the paper are applied to an illustrative case study. The guidelines set the basis of a more accurate, novel way of modeling water consumption impacts in LCA. The environmental relevance of this LCA impact category will improve, yet much research is needed to make the guidelines operational.

Understanding the LCA and ISO water footprint: A response to Hoekstra (2016) "A critique on the water-scarcity weighted water footprint in LCA".

Water footprinting has emerged as an important approach to assess water use related effects from consumption of goods and services. Assessment methods are proposed by two different communities, the Water Footprint Network (WFN) and the Life Cycle Assessment (LCA) community. The proposed methods are broadly similar and encompass both the computation of water use and its impacts, but differ in communication of a water footprint result. In this paper, we explain the role and goal of LCA and ISO-compatible water footprinting and resolve the six issues raised by Hoekstra (2016) in "A critique on the water-scarcity weighted water footprint in LCA". By clarifying the concerns, we identify both the overlapping goals in the WFN and LCA water footprint assessments and discrepancies between them. The main differing perspective between the WFN and LCA-based approach seems to relate to the fact that LCA aims to account for environmental impacts, while the WFN aims to account for water productivity of global fresh water as a limited resource. We conclude that there is potential to use synergies in research for the two approaches and highlight the need for proper declaration of the methods applied.

Immune quiescence of the brain is set by astroglial connexin 43.

In the normal brain, immune cell trafficking and immune responses are strictly controlled and limited. This unique homeostatic equilibrium, also called brain immune quiescence, is crucial to maintaining proper brain functions and is altered in various pathological processes, from chronic immunopathological disorders to cognitive and psychiatric impairments. To date, the precise nature of factors regulating the brain/immune system interrelationship is poorly understood. In the present study, we demonstrate that one of these regulating factors is Connexin 43 (Cx43), a gap junction protein highly expressed by astrocytes at the blood-brain barrier (BBB) interface. We show that, by setting the activated state of cerebral endothelium, astroglial Cx43 controls immune recruitment as well as antigen presentation mechanisms in the mouse brain. Consequently, in the absence of astroglial Cx43, recruited immune cells elaborate a specific humoral autoimmune response against the von Willebrand factor A domain-containing protein 5a, an extracellular matrix protein of the brain. Altogether, our results demonstrate that Cx43 is a new astroglial factor promoting the immune quiescence of the brain.

Immunoregulation at the gliovascular unit in the healthy brain: A focus on Connexin 43.

In the brain, immune cell infiltration is normally kept at a very low level and a unique microenvironment strictly restricts immune reactions and inflammation. Even in such quiescent environment, a constant immune surveillance is at work allowing the brain to rapidly react to threats. To date, knowledge about the factors regulating the brain-immune system interrelationship in healthy conditions remains elusive. Interestingly, astrocytes, the most abundant glial cells in the brain, may participate in many aspects of this unique homeostasis, in particular due to their close interaction with the brain vascular system and expression of a specific molecular repertoire. Indeed, astrocytes maintain the blood-brain barrier (BBB) integrity, interact with immune cells, and participate in the regulation of intracerebral liquid movements. We recently showed that Connexin 43 (Cx43), a gap junction protein highly expressed by astrocytes at the BBB interface, is an immunoregulating factor. The absence of astroglial Cx43 leads to a transient endothelial activation, a continuous immune recruitment as well as the development of a specific humoral autoimmune response against the von Willebrand factor A domain-containing protein 5a, an extracellular matrix protein expressed by astrocytes. In this review, we propose to gather current knowledge on how astrocytes may influence the immune system in the healthy brain, focusing on their roles at the gliovascular interface. We will also consider pathological situations involving astrocyte-specific autoimmunities. Finally, we will discuss the specific role of astroglial Cx43 and the physiological consequences of immune regulations taking place on inflammation, cognition and behavior in the absence of Cx43.

Hearing is normal without connexin30.

Gjb2 and Gjb6, two contiguous genes respectively encoding the gap junction protein connexin26 (Cx26) and connexin 30 (Cx30) display overlapping expression in the inner ear. Both have been linked to the most frequent monogenic hearing impairment, the recessive isolated deafness DFNB1. Although there is robust evidence for the direct involvement of Cx26 in cochlear functions, the contribution of Cx30 is unclear since deletion of Cx30 strongly downregulates Cx26 both in human and in mouse. Thus, it is imperative that any role of Cx30 in audition be clearly evaluated. Here, we developed a new Cx30 knock-out mouse model (Cx30(Δ/Δ)) in which half of Cx26 expression was preserved. Our results show that Cx30 and Cx26 coordinated expression is dependent on the spacing of their surrounding chromosomic region, and that Cx30(Δ/Δ) mutants display normal hearing. Thus, in deaf patients with GJB6 deletion as well as in the previous Cx30 knock-out mouse model, defective Cx26 expression is the likely cause of deafness, and in contrast to current opinion, Cx30 is dispensable for cochlear functions.

Prospective life cycle assessment of viticulture under climate change scenarios, application on two case studies in France.

Viticulture needs to satisfy consumers' demands for environmentally sound grape and wine production while envisaging adaptation options to diminish the impacts of projected climate change on future productivity. However, the impact of climate change and the adoption of adaptation levers on the environmental impacts of future viticulture have not been assessed. This study evaluates the environmental performance of grape production in two French vineyards, one located in the Loire Valley and another in Languedoc-Roussillon, under two climate change scenarios. First, the effect of climate-induced yield change on the environmental impacts of future viticulture was assessed based on grape yield and climate data sets. Second, besides the climate-induced yield change, this study accounted for the impacts of extreme weather events on grape yield and the implementation of adaptation levers based on the future probability and potential yield loss due to extreme events. The life cycle assessment (LCA) results associated with climate-induced yield change led to opposite conclusions for the two vineyards of the case study. While the carbon footprint of the vineyard from Languedoc-Roussillon is projected to increase by 29 % by the end of the century under the high emissions scenario (SSP5-8.5), the corresponding footprint is projected to decrease in the vineyard from the Loire Valley by approximately 10 %. However, when including the effect of extreme events and adaptation options, the life cycle environmental impacts of grape production are projected to drastically increase for both vineyards. For instance, under the SSP5-8.5 scenario, the carbon footprint for the vineyard of Languedoc-Roussillon is projected to increase fourfold compared to the current footprint, while it will rise threefold for the vineyard from the Loire Valley. The obtained LCA results emphasized the need to account for the impact of both climate change and extreme events on grape production under future climate change scenarios.

Generating environmental sampling and testing data for micro- and nanoplastics for use in life cycle impact assessment.

Ongoing efforts focus on quantifying plastic pollution and describing and estimating the related magnitude of exposure and impacts on human and environmental health. Data gathered during such work usually follows a receptor perspective. However, Life Cycle Assessment (LCA) represents an emitter perspective. This study examines existing data gathering and reporting approaches for field and laboratory studies on micro- and nanoplastics (MNPs) exposure and effects relevant to LCA data inputs. The outcomes indicate that receptor perspective approaches do not typically provide suitable or sufficiently harmonised data. Improved design is needed in the sampling, testing and recording of results using harmonised, validated and comparable methods, with more comprehensive reporting of relevant data. We propose a three-level set of requirements for data recording and reporting to increase the potential for LCA studies and models to utilise data gathered in receptor-oriented studies. We show for which purpose such data can be used as inputs to LCA, particularly in life cycle impact assessment (LCIA) methods. Implementing these requirements will facilitate proper integration of the potential environmental impacts of plastic losses from human activity (e.g. litter) into LCA. Then, the impacts of plastic emissions can eventually be connected and compared with other environmental issues related to anthropogenic activities.

The ribosome-associated protein RACK1 represses Kir4.1 translation in astrocytes and influences neuronal activity.

The regulation of translation in astrocytes, the main glial cells in the brain, remains poorly characterized. We developed a high-throughput proteomics screen for polysome-associated proteins in astrocytes and focused on ribosomal protein receptor of activated protein C kinase 1 (RACK1), a critical factor in translational regulation. In astrocyte somata and perisynaptic astrocytic processes (PAPs), RACK1 preferentially binds to a number of mRNAs, including Kcnj10, encoding the inward-rectifying potassium (K+) channel Kir4.1. By developing an astrocyte-specific, conditional RACK1 knockout mouse model, we show that RACK1 represses production of Kir4.1 in hippocampal astrocytes and PAPs. Upregulation of Kir4.1 in the absence of RACK1 increases astrocytic Kir4.1-mediated K+ currents and volume. It also modifies neuronal activity attenuating burst frequency and duration. Reporter-based assays reveal that RACK1 controls Kcnj10 translation through the transcript's 5' untranslated region. Hence, translational regulation by RACK1 in astrocytes represses Kir4.1 expression and influences neuronal activity.

In mice and humans, brain microvascular contractility matures postnatally.

Although great efforts to characterize the embryonic phase of brain microvascular system development have been made, its postnatal maturation has barely been described. Here, we compared the molecular and functional properties of brain vascular cells on postnatal day (P)5 vs. P15, via a transcriptomic analysis of purified mouse cortical microvessels (MVs) and the identification of vascular-cell-type-specific or -preferentially expressed transcripts. We found that endothelial cells (EC), vascular smooth muscle cells (VSMC) and fibroblasts (FB) follow specific molecular maturation programs over this time period. Focusing on VSMCs, we showed that the arteriolar VSMC network expands and becomes contractile resulting in a greater cerebral blood flow (CBF), with heterogenous developmental trajectories within cortical regions. Samples of the human brain cortex showed the same postnatal maturation process. Thus, the postnatal phase is a critical period during which arteriolar VSMC contractility required for vessel tone and brain perfusion is acquired and mature.

Transport mechanisms and fate of microplastics in estuarine compartments: A review.

Despite the importance of estuaries as transition zones between freshwater and marine compartments, their role in the transport of microplastics is still unclear. This review analyzes the findings pertaining to the transport mechanisms and other factors that influence the fate of microplastics in estuaries. It was found that the concentration of microplastics temporally varies under daily tides, monthly tides, and seasonal flows. Moreover, it spatially varies due to density effects, biofouling, aggregation, and salinity. Wind direction and intensity impact the spatiotemporal distribution of microplastics in the water column. Some of these processes transport microplastics to the estuarine sediments. Thereafter, microplastics are prone to resuspension by turbulence and bioturbation. Hence, estuaries act as temporary sinks that retain microplastics before being flushed to the ocean. Finally, a review of highly plastic-emitting rivers shows differences in the factors affecting the transport mechanisms of microplastics, which calls for regionalization when modelling their fate henceforward.

Reliability and validity of the Roche PD Mobile Application for remote monitoring of early Parkinson's disease.

Digital health technologies enable remote and therefore frequent measurement of motor signs, potentially providing reliable and valid estimates of motor sign severity and progression in Parkinson's disease (PD). The Roche PD Mobile Application v2 was developed to measure bradykinesia, bradyphrenia and speech, tremor, gait and balance. It comprises 10 smartphone active tests (with ½ tests administered daily), as well as daily passive monitoring via a smartphone and smartwatch. It was studied in 316 early-stage PD participants who performed daily active tests at home then carried a smartphone and wore a smartwatch throughout the day for passive monitoring (study NCT03100149). Here, we report baseline data. Adherence was excellent (96.29%). All pre-specified sensor features exhibited good-to-excellent test-retest reliability (median intraclass correlation coefficient = 0.9), and correlated with corresponding Movement Disorder Society-Unified Parkinson's Disease Rating Scale items (rho: 0.12-0.71). These findings demonstrate the preliminary reliability and validity of remote at-home quantification of motor sign severity with the Roche PD Mobile Application v2 in individuals with early PD.

Regional characterization of freshwater Use in LCA: modeling direct impacts on human health.

Life cycle assessment (LCA) is a methodology that quantifies potential environmental impacts for comparative purposes in a decision-making context. While potential environmental impacts from pollutant emissions into water are characterized in LCA, impacts from water unavailability are not yet fully quantified. Water use can make the resource unavailable to other users by displacement or quality degradation. A reduction in water availability to human users can potentially affect human health. If financial resources are available, there can be adaptations that may, in turn, shift the environmental burdens to other life cycle stages and impact categories. This paper proposes a model to evaluate these potential impacts in an LCA context. It considers the water that is withdrawn and released, its quality and scarcity in order to evaluate the loss of functionality associated with water uses. Regionalized results are presented for impacts on human health for two modeling approaches regarding affected users, including or not domestic uses, and expressed in disability-adjusted life years (DALY). A consumption and quality based scarcity indicator is also proposed as a midpoint. An illustrative example is presented for the production of corrugated board with different effluents, demonstrating the importance of considering quality, process effluents and the difference between the modeling approaches.

Evaluation of sector-specific AWARE characterization factors for water scarcity footprint of electricity generation.

Life Cycle Impact Assessment (LCIA) links the emissions and resource abstractions of a product system or process to potential impacts on the environment through characterization factors (CF). For regionalized impact categories like water-use, the regional CFs can vary over several orders of magnitude within the same country. The aggregated country-level CF, often used in LCIA, represents an average of local CF weighted by the local water consumption of all (or most) human water use including water use by all (or most) economic sectors. There is, however, great variability in spatio-temporal distribution of human water consumption across different industries. This study provides industry-specific water-use CFs for the electricity sector across the US. Our analysis shows that for electricity generation, the use of all-sector aggregated water-use CF would lead to an underestimation of impact scores compared to industry-specific CFs, by two folds. Even within the electricity sector, for two of the major subsectors, electricity based on natural gas and hydroelectricity, the country-level CFs can be significantly different due to the geographic distribution of powerplants. Our findings signify that the use of industry-specific CF can have a high influence in LCIA, especially for impact categories, such as water-use, with great spatio-temporal heterogeneity.