Alcohol最新文献

{"title":"Pain and alcohol consumption among people living with HIV: examining the moderating roles of depression and social support","authors":"Nadine R. Taghian ,&nbsp;Tibor P. Palfai ,&nbsp;Michael R. Winter ,&nbsp;Theresa W. Kim ,&nbsp;Kara M. Magane ,&nbsp;Richard Saitz ,&nbsp;Michael D. Stein","doi":"10.1016/j.alcohol.2025.07.002","DOIUrl":"10.1016/j.alcohol.2025.07.002","url":null,"abstract":"<div><div>Pain and heavy alcohol use are common among people living with HIV (PLWH), and influence one another, potentially exacerbating these conditions over time. This study examines the prospective association between pain and alcohol use among PLWH with a history of unhealthy drinking behaviors and/or substance use and tests whether depression and social support are moderators. A sample of 233 participants from the Boston Alcohol Research Collaborative on HIV/AIDS cohort completed measures of pain intensity (i.e., average severity of pain in the past week) and pain interference (i.e., average interference of pain in everyday life), heavy episodic drinking, number of drinks, social support and depression at baseline and 6 months later. Negative binomial regression analyses assessed whether pain at baseline predicted alcohol use at 6 months, and examined baseline social support and depression as moderators. Pain intensity was significantly associated with number of drinks (IRR = 1.80, 95 % CI: 1.05, 3.08) but not number of heavy drinking days (IRR = 1.84, 95 % CI: 0.83, 4.07), while pain interference was not associated with number of drinks (IRR = 1.63, 95 % CI: 0.96, 2.75) nor heavy drinking days (IRR = 1.43, 95 % CI: 0.64, 3.17) at six months. Neither social support, nor depression were significant moderators of the association between pain and 6-month alcohol use outcomes. Pain intensity is prospectively associated with more alcohol use, but not with heavy drinking among PLWH. We conclude that pain is an important factor to address when considering interventions to reduce alcohol use among PLWH.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"128 ","pages":"Pages 13-20"},"PeriodicalIF":2.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol, aging, and the gut microbiome: Intersections of immunity, barrier dysfunction, and disease","authors":"Esther Melamed ,&nbsp;Wiramon Rungratanawanich ,&nbsp;Suthat Liangpunsakul ,&nbsp;Katherine A. Maki ,&nbsp;Rebecca L. McCullough ,&nbsp;Cristina Llorente","doi":"10.1016/j.alcohol.2025.07.001","DOIUrl":"10.1016/j.alcohol.2025.07.001","url":null,"abstract":"<div><div>Alcohol consumption exerts complex, dose- and context-dependent effects on human health, particularly by influencing the gut microbiome, intestinal barrier integrity, immune regulation, and aging processes. Genetic variation and advancing age are two major, and often interacting, factors that modify the risk of alcohol-related diseases. Among genetic factors, the prevalent aldehyde dehydrogenase 2 polymorphism (ALDH2∗2) compromises acetaldehyde clearance, driving toxic metabolite accumulation, oxidative stress, and increased intestinal permeability that disrupts gut microbial communities, even at low levels of alcohol consumption. Heavy and chronic alcohol use further disrupts gut microbial communities, erodes mucosal integrity, and drives systemic inflammation, contributing to alcohol-associated liver disease (ALD), neuroinflammation, and multi-organ injury. Aging independently worsens these effects by promoting chronic low-grade inflammation and impaired immune responses, heightening susceptibility to alcohol-induced pathology. In specific contexts, such as certain autoimmune diseases, low to moderate alcohol intake may exert immunomodulatory effects and influence the gut microbiome, potentially contributing to reduced inflammation and alterations in microbial composition. This review synthesizes current mechanistic insights into how alcohol, host genetics, the gut microbiome, immune regulatory pathways, and aging intersect to influence disease risk. As global populations age and the burden of alcohol-related health issues rises, there is an urgent need for integrated, systems-level approaches. Future research should prioritize precision-based, gut-targeted strategies aimed at restoring microbial balance, maintaining intestinal barrier integrity, and mitigating alcohol-related harm across the lifespan.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"128 ","pages":"Pages 1-12"},"PeriodicalIF":2.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explaining increased efficacy of naltrexone in the treatment of alcohol dependent patients with a family history of alcohol use disorder: A systematic review on the role of reward sensitivity and sweet liking","authors":"Jan van Amsterdam ,&nbsp;Wim van den Brink","doi":"10.1016/j.alcohol.2025.06.004","DOIUrl":"10.1016/j.alcohol.2025.06.004","url":null,"abstract":"<div><div>A positive family history of alcohol use disorder (FHA+) is one of the strongest risk factors for developing alcohol use disorder (AUD) compared. Importantly, naltrexone (NTX) has shown higher efficacy in treating FHA + AUD patients than FHA− AUD patients. Possibly, this may be explained by the attenuation of high reward sensitivity and liking sweet substances (“sweet liking”; SL) in FHA + AUD patients. This systematic review explores whether attenuation by NTX of reward sensitivity and SL explains its higher efficacy in FHA + compared to FHA− AUD patients.</div><div>Separate systematic literature searches were performed on the effect of NTX in FHA + AUD patients, the effect of NTX on reward sensitivity, and the associations of FHA+ with reward sensitivity and SL.</div><div>In total, 36 eligible studies were included (6 for the effect of NTX in FHA + AUD patients, 18 for reward sensitivity, and 12 for sweet liking). In 5 out of 6 studies, a moderating effect of FHA + on NTX treatment efficacy in AUD was shown, with higher efficacy of NTX in FHA + AUD patients. In 6 out of 8 studies, reward sensitivity moderated the treatment effect of NTX in AUD, and in 9 of 10 studies, reward sensitivity was attenuated by NTX. In 3 studies, SL positively moderated the effect of NTX in AUD. Finally, in 9 of 9 studies, SL was attenuated by NTX and enhanced by (partial) opioid agonists.</div><div>Increased reward sensitivity (and sweet-liking as its possible indicator) appeared to be positively associated with FHA+ and was attenuated by NTX, which may (partly) explain the increased effect of NTX in FHA + AUD patients. These results may foster personalized pharmacotherapy in AUD patients.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"127 ","pages":"Pages 63-72"},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of physical pain, alcohol use, and related factors in the daily lives of patients with chronic low back pain","authors":"Ian A. McNamara ,&nbsp;Jeff Boissoneault ,&nbsp;Jarrod M. Ellingson ,&nbsp;Jake Sauer ,&nbsp;Ryan W. Carpenter","doi":"10.1016/j.alcohol.2025.06.002","DOIUrl":"10.1016/j.alcohol.2025.06.002","url":null,"abstract":"<div><h3>Background</h3><div>Alcohol use and chronic pain are highly prevalent, costly, and have a bidirectional relationship. This may occur, in part, because of the analgesic effects of alcohol. Specifically, individuals may drink alcohol to address both physical pain and the subsequent increases in negative affect that may be brought on by painful experiences. The current project examined the Catastrophizing, Anxiety, Negative Urgency, and Expectancy (CANUE) model in daily life to better understand the association between alcohol use and pain.</div></div><div><h3>Methods</h3><div>Hypothesized paths of the CANUE model were examined using intensive longitudinal data (n = 34; total n_observations = 2960) collected using ecological momentary assessment over fourteen days from patients with chronic lower back pain who reported drinking alcohol (n_{drinking episodes} = 5.88). Multilevel models examined associations of pain, negative affect, and alcohol use, as well as potential moderators (pain-related cognitions, alcohol expectancies, and impulsivity) of these associations.</div></div><div><h3>Results</h3><div>Previous-occasion physical pain, but not cumulative-average pain, and pain-related alcohol expectancies, were associated with a greater likelihood of alcohol use. Though there was no main effect of cumulative-average negative affect on alcohol use, negative affect interacted with impulsivity, such that participants were more likely to continue drinking when experiencing increased negative affect and impulsivity. Results did not find a hypothesized indirect effect of pain on alcohol use via negative affect. Alcohol use was associated with reduced next-occasion pain and increased perceptions of alcohol-related pain relief.</div></div><div><h3>Discussion</h3><div>While cumulative-average pain was not associated with an increased likelihood of drinking, individuals were more likely to drink after occasions of elevated pain. This may indicate that participants drank to reduce pain, as was also suggested by the association between pain-related alcohol expectancies and drinking. This is one of the first studies to examine associations of alcohol use and chronic pain in daily life. The results provide evidence for the importance of pain as an antecedent to alcohol use. Findings supported some components of the CANUE model but also highlight the need for further investigation to inform potential revision of the mode.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"127 ","pages":"Pages 73-83"},"PeriodicalIF":2.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol use disorder exacerbates clinical and vascular risks differentially in psychiatric disorders","authors":"Eva Christina Meyer ,&nbsp;Younes Adam Tabi","doi":"10.1016/j.alcohol.2025.06.003","DOIUrl":"10.1016/j.alcohol.2025.06.003","url":null,"abstract":"<div><div>Alcohol Use Disorder (AUD) is a major public health concern with detrimental effects on cognitive and neurological function, yet its impact on psychiatric populations remains incompletely defined. In this global propensity score–matched cohort study, we examined the clinical and vascular consequences of comorbid alcohol abuse across diverse psychiatric disorders. Data from the TriNetX network, encompassing electronic medical records from 143 healthcare organizations, were analyzed. For each disorder—anxiety, depression, bipolar disorder, schizophrenia, reaction to severe stress, eating disorders, personality disorders, psychoactive substance dependence, developmental disorders, and obsessive-compulsive disorder—patients with alcohol abuse were matched 1:1 to those without, controlling for demographic and clinical factors. Over a 1095-day follow-up, outcomes evaluated included emergency department visits, pain prevalence, mortality, and cerebrovascular events (transient ischemic attacks and strokes). Alcohol abuse was consistently associated with significantly higher emergency care utilization, increased somatic pain, and elevated mortality across all groups. For instance, anxiety and depression cohorts exhibited 8.1% and 7.3% higher emergency visits and increased mortality by 2.7% and 2.4%, respectively, while schizophrenia showed a twofold increase in stroke risk and markedly higher pain (risk ratio 2.21). These results underscore that AUD exacerbates clinical and vascular risks in psychiatric patients, highlighting the urgent need for targeted interventions.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"127 ","pages":"Pages 85-92"},"PeriodicalIF":2.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examining the moderating role of intolerance of uncertainty on pain tolerance and craving in patients with chronic pain and alcohol use disorder","authors":"Milena Radoman ,&nbsp;Emily Heilner ,&nbsp;Colleen McGowan ,&nbsp;Benazir Neree-Thompson ,&nbsp;Elcin Sakmar ,&nbsp;Rajita Sinha","doi":"10.1016/j.alcohol.2025.06.001","DOIUrl":"10.1016/j.alcohol.2025.06.001","url":null,"abstract":"<div><div>Chronic pain (CP) and alcohol use disorder (AUD) frequently co-occur, yet the psychological factors underlying their interaction remain unclear. Intolerance of uncertainty (IU) – a cognitive trait linked to distress in unpredictable situations – may influence pain management and coping behaviors in these populations. This study examined whether IU moderates pain and alcohol craving responses to a pain-related stressor in individuals with CP and AUD. Fifty-five adults aged 18–65 years were enrolled, including individuals with CP only (n = 20), AUD only (n = 14), CP + AUD (n = 8), and healthy controls (n = 13). Participants completed a self-report measure of IU and the Yale Pain Stress Test (YPST), an adaptation of the Cold Pressor Test, designed to elicit pain-related stress. Behavioral pain tolerance, subjective pain and alcohol craving were assessed across two experimental sessions, one with exposure to an ice-cold water stressor and the second with a warm-water control condition. Exposure to the pain-related stressor significantly reduced behavioral pain tolerance and increased subjective pain across all groups, and also heightened alcohol craving, particularly in individuals with AUD. IU moderated the pain experience during pain-related stress: in the CP + AUD group, higher IU was associated with lower pain tolerance, whereas in the AUD group, higher IU was correlated with greater pain tolerance. IU also moderated craving responses, with higher IU predicting increased craving in individuals with both CP and AUD. These preliminary findings highlight IU as a potential treatment target, suggesting that interventions aimed at improving uncertainty tolerance may enhance pain coping and reduce stress-driven alcohol-seeking behaviors in vulnerable populations.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"127 ","pages":"Pages 55-61"},"PeriodicalIF":2.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating TWAS and GWAS identifies gut microbiota–immune interactions to alcohol dependence genetics in European sample","authors":"Haohao Xu ,&nbsp;Peng Shen ,&nbsp;Zhenglin Zhao ,&nbsp;Yushuang Xing ,&nbsp;Tonghui Yi ,&nbsp;Chao Yang ,&nbsp;Han Gao ,&nbsp;Hongyan Guo ,&nbsp;Mingqian Zhao ,&nbsp;Shanbo Zhang ,&nbsp;Di Jia ,&nbsp;Weiming Zhao","doi":"10.1016/j.alcohol.2025.05.006","DOIUrl":"10.1016/j.alcohol.2025.05.006","url":null,"abstract":"<div><h3>Objective</h3><div>Alcohol dependence (AD) is a global public health concern with strong genetic characteristics. The purpose of this study was to explore the underlying pathogenic genes and mechanisms associated with AD.</div></div><div><h3>Methods</h3><div>This study employed a multi-omics Mendelian randomization approach to identify potential disease-causing genes for AD. Specifically, we integrated transcriptome-wide association studies (TWAS) with summary-data-based Mendelian randomization (SMR) to pinpoint candidate genes associated with AD. Additionally, mediating Mendelian randomization was utilized to investigate the mediating role of the gut microbiota in the relationship between immune cell phenotypes and AD.</div></div><div><h3>Results</h3><div>Two susceptibility genes associated with AD, ADH1C and POLI, were identified a joint analysis of SMR and integrated cross-tissue and single tissue TWAS in European population. A new genetic locus associated with AD, rs62307318, was uncovered through cross-organism TWAS. This finding was further validated using Mendelian randomization and Phenome-wide association analysis. Additionally, Mendelian randomization identified Paceibacteria as a possible mediator between Myeloid DC AC and AD.</div></div><div><h3>Conclusion</h3><div>This study identified two genes closely related to AD and explored the possible pathogenesis of AD, which provides a new insight into the treatment and pathogenesis of AD.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"127 ","pages":"Pages 11-20"},"PeriodicalIF":2.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol effects on associative and sensorimotor cortico-thalamo-basal ganglia circuits alter decision making and alcohol intake","authors":"David M. Lovinger","doi":"10.1016/j.alcohol.2025.05.005","DOIUrl":"10.1016/j.alcohol.2025.05.005","url":null,"abstract":"<div><div>Much of the behavioral repertoire of humans and other vertebrates is learned and controlled through the function of brain circuits involving the cortex, thalamus and Basal Ganglia (for simplicity we will refer to this as the Cortico-Thalamo-Basal Ganglia, or CTBG, circuitry). As the name implies, these circuits include the different regions of cortex and thalamus, as well as BG subregions including the striatum, globus pallidus (GP), substantia nigra (SN)/ventral tegmental area (VTA), and the subthalamic nucleus (STN). This circuitry has developed evolutionarily to provide overarching control of actions following discrete environmental events as well as self-initiated actions. Several parallel CTBG circuits have been identified and linked to different aspects of action control under different circumstances. Research in experimental psychology and Neuroscience has established how different CTBG circuits contribute to control of actions based on environmental circumstances and past learning history. There is also a large and growing body of evidence that misused substances, including alcohol, act on cells within these circuits. These actions promote acute intoxication and drug seeking and contribute to changes in behavior induced by chronic alcohol exposure, withdrawal and relapse. Alcohol exposure also influences which of the different CTBG circuits has the strongest influence on behavior. This review will cover the relevant circuitry and describe the current state of knowledge as to how alcohol alters CTBG circuit function and control of behavior. Studies in rodents, non-human primates and humans will be discussed. Finally, ideas for future research directions in this area will be considered.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"127 ","pages":"Pages 21-46"},"PeriodicalIF":2.5,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain in comorbid alcohol use disorder and HIV: A network meta-analysis study","authors":"Muhammed Bishir,&nbsp;Mohamed Sheik Tharik Abdul Azeeze,&nbsp;Sulie L. Chang","doi":"10.1016/j.alcohol.2025.05.003","DOIUrl":"10.1016/j.alcohol.2025.05.003","url":null,"abstract":"<div><div>Alcohol use is prevalent among people with HIV (PWH). PWH often experience pain (said discomfort) and use alcohol to combat pain. We reported that short-term alcohol exposure exerts analgesic effect. Prolonged exposure is known to result in chronic pain. We hypothesize that alcohol exposure, either <em>in-vivo</em> for <em>macaques</em> or <em>in-silico</em> simulation exposure onto differentially expressed genes (DEGs) from HIV-1Tg rats and HIV patients, exacerbates discomfort in PWH. To substantiate this hypothesis, we analyzed genomic data collected from three brain datasets including the hippocampus of alcohol-exposed <em>Macaca mulatta</em> (GSE69685), HIV-1Tg rats (GSE47474), and post-mortem brain tissue of HIV-positive patients (GSE28160). Ingenuity Pathway Analysis (IPA)-Core Analysis revealed activation of neuroinflammation, neuropathic pain signaling pathways, and the inhibition of opioid signaling as well as in the increase of neuromuscular disease with neuropathy in <em>Macaca mulatta</em> exposed to binge EtOH and SIV infection. IPA-Core Analysis of the DEGs from HIV-1Tg rats, a rat model that mimics HIV patients on cART, possessing 7 of 9 HIV viral proteins, showed activation of neuroinflammation, neuropathic pain signaling pathways. IPA-Core Analysis of the DEGs from HIV patients showed activation of neuroinflammation and inhibition of neuropathic pain and increase in neuromuscular disease with neuropathy. To study the impact of alcohol exposure in HIV-1Tg rats and HIV patients, <em>in-silico</em> simulation of ethanol (EtOH) treatment mimicking exposure of alcohol onto the DEGs in response to HIV viral proteins in HIV-1Tg rats and HIV infection in HIV patients enhanced discomfort and increased neuromuscular diseases. These molecules showed significant modulation by simulated alcohol exposure, further supporting the link between alcohol use and heightened pain in PWH. Taking together, our findings suggest that alcohol consumption and HIV promote pain via modulating signaling pathways including neuroinflammation, and neuropathic pain signaling pathways and by disease like neuromuscular disease with neuropathy.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"126 ","pages":"Pages 43-53"},"PeriodicalIF":2.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol consumption during early adulthood increases the vulnerability of locus coeruleus neurons and amyloid beta pathology in female APP/PS1 mice","authors":"Shaydel Engel,&nbsp;Madison Dillerud,&nbsp;Matthew Scalf,&nbsp;Ruth Dobbelmann,&nbsp;Yijuan Du,&nbsp;Anna M. Lee,&nbsp;Steven M. Graves","doi":"10.1016/j.alcohol.2025.05.004","DOIUrl":"10.1016/j.alcohol.2025.05.004","url":null,"abstract":"<div><div>Alcohol use disorder is the most common substance misuse disorder and Alzheimer's disease (AD) is the most common neurodegenerative disease. Evidence suggests that alcohol consumption may increase the risk for developing dementia and AD. The locus coeruleus (LC) is a region wherein the impact of alcohol and AD may converge. The LC is a noradrenergic nucleus that is highly vulnerable to degeneration in AD, and loss of LC neurons is associated with increased amyloid beta (Abeta) pathology. The present study examined whether alcohol consumption during early adulthood impacts LC degeneration and Abeta using the APP/PS1 mouse model. Female APP/PS1 mice underwent an eight-week chronic intermittent access (IA) alcohol consumption paradigm followed by twenty-three weeks of abstinence; water-consuming control subjects were run in parallel. APP/PS1 mice that had IA to alcohol showed a 21.9% decrease in the number of LC neurons and a decrease in the length of noradrenergic axons innervating the primary motor cortex. Furthermore, this alcohol induced LC deficit was associated with an increase in Abeta pathology in the primary motor cortex. In contrast to results from female APP/PS1 mice, there were no deficits in axon length and only a 9.4% decrease in the number of LC neurons in non-transgenic female subjects after abstinence from IA to alcohol. Our results demonstrate that alcohol consumption during early adulthood increases the vulnerability of LC neurons to degeneration and exacerbates Abeta pathology in female APP/PS1 mice, providing evidence that a history of alcohol abuse may impact the trajectory and severity of AD.</div></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":"127 ","pages":"Pages 1-9"},"PeriodicalIF":2.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}