A biomarker signature to predict complete response to itacitinib and corticosteroids in acute graft-versus-host disease.

A broad proteomic analysis was conducted to identify and evaluate candidate biomarkers potentially predictive of response to treatment with an oral selective Janus kinase 1 (JAK1) inhibitor, itacitinib, in acute graft-versus-host disease (GVHD). Plasma samples from 25 participants (identification cohort; NCT02614612) were used to identify novel biomarkers that were tested in a validation cohort from a placebo-controlled, randomised trial (n = 210; NCT03139604). The identification cohort received corticosteroids plus 200 or 300 mg itacitinib once daily. The validation cohort received corticosteroids plus 200 mg itacitinib once daily or placebo. A broad proteomic analysis was conducted using a proximity extension assay. Baseline and longitudinal comparisons were performed with unpaired t-test and one-way analysis of variance used to evaluate biomarker level changes. Seven candidate biomarkers were identified. Monocyte-chemotactic protein (MCP)3, pro-calcitonin/calcitonin (ProCALCA/CALCA), together with a previously identified prognostic acute GVHD biomarker, regenerating islet-derived protein (REG)3A, stratified complete responders from non-responders (participants with progressive disease) to itacitinib, but not placebo, potentially representing predictive biomarkers of itacitinib in acute GVHD. ProCALCA/CALCA, suppressor of tumorigenicity (ST)2, and tumour necrosis factor receptor (TNFR)1 were significantly reduced over time by itacitinib in responders, potentially representing response-to-treatment biomarkers. Novel biomarkers have the potential to identify patients with acute GVHD that may respond to itacitinib plus corticosteroid treatment (NCT02614612; NCT03139604).

Interplay between Humoral and CLA+ T Cell Response against Candida albicans in Psoriasis.

Candida albicans (CA) infections have been associated with psoriasis onset or disease flares. However, the integrated immune response against this fungus is still poorly characterized in psoriasis. We studied specific immunoglobulins in plasma and the CA response in cocultures of circulating memory CD45RA- cutaneous lymphocyte antigen (CLA)+/- T cell with autologous epidermal cells from plaque and guttate psoriasis patients (cohort 1, n = 52), and also healthy individuals (n = 17). A complete proteomic profile was also evaluated in plaque psoriasis patients (cohort 2, n = 114) regarding their anti-CA IgA levels. Increased anti-CA IgA and IgG levels are present in the plasma from plaque but not guttate psoriasis compared to healthy controls. CA cellular response is confined to CLA+ T cells and is primarily Th17. The levels of anti-CA IgA are directly associated with CLA+ Th17 response in plaque psoriasis. Proteomic analysis revealed distinct profiles in psoriasis patients with high anti-CA IgA. C-C motif chemokine ligand 18, chitinase-3-like protein 1 and azurocidin were significantly elevated in the plasma from plaque psoriasis patients with high anti-CA levels and severe disease. Our results indicate a mechanism by which Candida albicans exposure can trigger a clinically relevant IL-17 response in psoriasis. Assessing anti-CA IgA levels may be useful in order to evaluate chronic psoriasis patients.

Clinicogenomic Analysis of FGFR2-Rearranged Cholangiocarcinoma Identifies Correlates of Response and Mechanisms of Resistance to Pemigatinib.

Pemigatinib, a selective FGFR1-3 inhibitor, has demonstrated antitumor activity in FIGHT-202, a phase II study in patients with cholangiocarcinoma harboring FGFR2 fusions/rearrangements, and has gained regulatory approval in the United States. Eligibility for FIGHT-202 was assessed using genomic profiling; here, these data were utilized to characterize the genomic landscape of cholangiocarcinoma and to uncover unique molecular features of patients harboring FGFR2 rearrangements. The results highlight the high percentage of patients with cholangiocarcinoma harboring potentially actionable genomic alterations and the diversity in gene partners that rearrange with FGFR2. Clinicogenomic analysis of pemigatinib-treated patients identified mechanisms of primary and acquired resistance. Genomic subsets of patients with other potentially actionable FGF/FGFR alterations were also identified. Our study provides a framework for molecularly guided clinical trials and underscores the importance of genomic profiling to enable a deeper understanding of the molecular basis for response and nonresponse to targeted therapy. SIGNIFICANCE: We utilized genomic profiling data from FIGHT-202 to gain insights into the genomic landscape of cholangiocarcinoma, to understand the molecular diversity of patients with FGFR2 fusions or rearrangements, and to interrogate the clinicogenomics of patients treated with pemigatinib. Our study highlights the utility of genomic profiling in clinical trials.This article is highlighted in the In This Issue feature, p. 211.

Transcriptomic analysis of hidradenitis suppurativa skin suggests roles for multiple inflammatory pathways in disease pathogenesis.

OBJECTIVE: Hidradenitis suppurativa (HS) is a chronic inflammatory disease with limited treatment options; therefore, the current study investigated the downstream signaling pathways that are differentially expressed in HS subjects and may drive disease pathogenesis. METHODS: The expression of 144 genes was evaluated in the skin of 16 healthy subjects and 34 subjects with mild to severe HS using QuantiGene Plex assay. RESULTS: One hundred and twenty-nine genes were significantly elevated in lesional HS skin as compared to the skin of healthy controls including pro-inflammatory cytokines (IL-1α, IL-6, TNF-α), IL-17-associated cytokines (IL-17A, IL-17F, IL-23A), the IL-10 family of cytokines (IL-10, IL-19, IL-20, IL-22, IL-24), and IFN family members (IFNA1, IFNB1, IFNG, IL-12B). This corresponded with increased expression of tyrosine kinases (JAK1, JAK3, BTK, SYK) and their downstream signaling partners (STAT1, STAT2, STAT3, STAT5A, STAT5B, STAT6). CONCLUSION: These data illustrate the diverse immune activation in lesional HS skin and suggest that deeper interrogation of the disease heterogeneity may reveal unique opportunities for targeted therapies in designated subpopulations.

Galectin-3 as a Predictor of Long-term Survival After Isolated Coronary Artery Bypass Grafting Surgery.

BACKGROUND: Galectin-3 (Gal-3) is a well-established biomarker of adverse clinical outcomes, but its prognostic value for long-term survival after cardiac surgery is not well understood. Elevated levels of Gal-3 have been found to be remarkably associated with higher risk of death in both acute decompensated and chronic heart failure populations. Its prognostic value for long-term survival after cardiac surgery is not known. METHODS: A sample of patients contributing to the Northern New England Cardiovascular Disease Study Group Cardiac Surgery Registry from 2004 to 2007 were enrolled in a prospective biomarker cohort (N = 1690). Preoperative Gal-3 levels were measured and categorized by quartile. We used Kaplan-Meier survival analysis and Cox regression models, adjusting for variables in The Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategy probability calculator to evaluate the association between elevated Gal-3 levels and survival to 6 years. RESULTS: Preoperative Gal-3 levels ranged from 1.72 to 28.89 ng/mL (mean, 8.96 ng/mL; median, 8.06 ng/mL; interquartile range, 5.42-11.08 ng/mL). Crude survival decreased by increasing quartile. After adjustment, serum levels of Gal-3 in the highest quartile of the cohort were associated with significantly decreased survival compared with the lowest quartile (hazard ratio [HR] 2.22; 95% confidence interval [CI], 1.40-3.54; P = .001). No decrease in survival was found for the middle quartiles (HR 1.36; 95% CI, 0.87-2.12; P = .177). CONCLUSIONS: A substantial association was found between elevated preoperative Gal-3 levels and risk of mortality after isolated coronary artery bypass grafting surgery. An assessment of the relationship between preoperative serum biomarkers and long-term survival can be used for risk stratification or estimating postsurgical prognosis.

Influence of Work Characteristics on the Association Between Police Stress and Sleep Quality.

BACKGROUND: Police officers' stress perception, frequency of stressful events (stressors), and police work characteristics may contribute to poor sleep quality through different mechanisms. METHODS: We investigated associations of stress severity (measured by stress rating score) and frequency of stressors with sleep quality and examined the influence of police work characteristics including workload, police rank, prior military experience, and shift work on the associations. Participants were 356 police officers (256 men and 100 women) enrolled in the Buffalo Cardio-Metabolic Occupational Police Stress Study from 2004 to 2009. A mean stress rating score and mean frequency of stressors occurring in the past month were computed for each participant from the Spielberger Police Stress Survey data. Sleep quality was assessed using the global score derived from the Pittsburgh Sleep Quality Index survey. Linear associations of the stress rating score and frequency of stressors with sleep quality (Pittsburgh Sleep Quality Index global score) were tested. Age, sex, race/ethnicity, and smoking status were selected as potential confounders. RESULTS: The stress rating score was positively and independently associated with poor sleep quality (ß = 0.17, p = 0.002). Only workload significantly modified this association (ß = 0.23, p = 0.001 for high workload group; p-interaction = 0.109). The frequency of stressors was positively and independently associated with poor sleep quality (ß = 0.13, p = 0.025). Only police rank significantly modified the association (ß = 0.007, p = 0.004 for detectives/other executives; p-interaction = 0.076). CONCLUSION: Both police officers' perception of stress severity and the frequency of stressors are associated with poor sleep quality. Stress coping or sleep promotion regimens may be more beneficial among police officers reporting high workloads.

The Association between Cytokines and 365-Day Readmission or Mortality in Adult Cardiac Surgery.

Cardiac surgery results in a multifactorial systemic inflammatory response with inflammatory cytokines, such as interleukin-10 and 6 (IL-10 and IL-6), shown to have potential in the prediction of adverse outcomes including readmission or mortality. This study sought to measure the association between IL-6 and IL-10 levels and 1-year hospital readmission or mortality following cardiac surgery. Plasma biomarkers IL-6 and IL-10 were measured in 1,047 patients discharged alive after isolated coronary artery bypass graft surgery from eight medical centers participating in the Northern New England Cardiovascular Disease Study Group between 2004 and 2007. Readmission status and mortality were ascertained using Medicare, state all-payer claims, and the National Death Index. We evaluated the association between preoperative and postoperative cytokines and 1-year readmission or mortality using Kaplan-Meier estimates and Cox's proportional hazards modeling, adjusting for covariates used in the Society of Thoracic Surgeons 30-day readmission model. The median follow-up time was 1 year. After adjustment, patients in the highest tertile of postoperative IL-6 values had a significantly increased risk of readmission or death within 1 year (HR: 1.38; 95% CI: 1.03-1.85), and an increased risk of death within 1 year of discharge (HR: 4.88; 95% CI: 1.26-18.85) compared with patients in the lowest tertile. However, postoperative IL-10 levels, although increasing through tertiles, were not found to be significantly associated independently with 1-year readmission or mortality (HR: 1.25; 95% CI: .93-1.69). Pro-inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10 may be postoperative markers of cardiac injury, and IL-6, specifically, shows promise in predicting readmission and mortality following cardiac surgery.

Elevated preoperative Galectin-3 is associated with acute kidney injury after cardiac surgery.

BACKGROUND: Previous research suggests that novel biomarkers may be used to identify patients at increased risk of acute kidney injury following cardiac surgery. The purpose of this study was to evaluate the relationship between preoperative levels of circulating Galectin-3 (Gal-3) and acute kidney injury after cardiac surgery. METHODS: Preoperative serum Gal-3 was measured in 1498 patients who underwent coronary artery bypass graft (CABG) surgery and/or valve surgery as part of the Northern New England Biomarker Study between 2004 and 2007. Preoperative Gal-3 levels were measured using multiplex assays and grouped into terciles. Univariate and multinomial logistic regression was used to assess the predictive ability of Gal-3 terciles and AKI occurrence and severity. RESULTS: Before adjustment, patients in the highest tercile of Gal-3 had a 2.86-greater odds of developing postoperative KDIGO Stage 2 or 3 (p < 0.001) and 1.70-greater odds of developing KDIGO Stage 1 (p = < 0.001), compared to the first tercile. After adjustment, patients in the highest tercile had 2.95-greater odds of developing KDIGO Stage 2 or 3 (p < 0.001) and 1.71-increased odds of developing KDIGO Stage 1 (p = 0.001), compared to the first tercile. Compared to the base model, the addition of Gal-3 terciles improved discriminatory power compared to without Gal-3 terciles (test of equality = 0.042). CONCLUSION: Elevated preoperative Gal-3 levels significantly improves predictive ability over existing clinical models for postoperative AKI and may be used to augment risk information for patients at the highest risk of developing AKI and AKI severity after cardiac surgery.

The Association Between Novel Biomarkers and 1-Year Readmission or Mortality After Cardiac Surgery.

BACKGROUND: Novel cardiac biomarkers including soluble suppression of tumorigenicity 2, galectin-3, and the N-terminal prohormone of brain natriuretic peptide may be associated with long-term adverse outcomes after cardiac surgery. We sought to measure the association between cardiac biomarker levels and 1-year hospital readmission or mortality. METHODS: Plasma biomarkers from 1,047 patients discharged alive after isolated coronary artery bypass graft surgery from 8 medical centers were measured in a cohort from the Northern New England Cardiovascular Disease Study Group between 2004 and 2007. We evaluated the association between preoperative and postoperative biomarkers and 1-year readmission or mortality using Kaplan-Meier estimates and Cox proportional hazards modeling, adjusting for covariates used in The Society of Thoracic Surgeons 30-day readmission model. RESULTS: The median follow-up time was 365 days. After adjustment for established risk factors, above-median levels of postoperative galectin-3 (median 10.35 ng/mL; hazard ratio, 1.40; 95% confidence interval, 1.08 to 1.80; p = 0.010) and N-terminal prohormone of brain natriuretic peptide (median = 15.21 ng/mL, hazard ratio, 1.42; 95% confidence interval, 1.07 to 1.87; p = 0.014) were each significantly associated with 1-year readmission or mortality. CONCLUSIONS: In patients undergoing cardiac surgery, novel cardiac biomarkers were associated with readmission or mortality independent of established risk factors. Measurement of these biomarkers may improve our ability to identify patients at highest risk for readmission or mortality before discharge. This will also allow resource allocation accordingly, while implementing strategies for personalized medicine based on the biomarker profile of the patient.

Preoperative serum ST2 level predicts acute kidney injury after adult cardiac surgery.

OBJECTIVE: The purpose of this study was to evaluate the relationship between preoperative levels of serum soluble ST2 (ST2) and acute kidney injury (AKI) after cardiac surgery. Previous research has shown that biomarkers facilitate the prediction of AKI and other complications after cardiac surgery. METHODS: Preoperative ST2 proteins were measured in 1498 patients undergoing isolated coronary artery bypass graft surgery at 8 hospitals participating in the Northern New England Biomarker Study from 2004 to 2007. AKI severity was defined using the Acute Kidney Injury Network (AKIN) definition. Preoperative ST2 levels were measured using multiplex assays. Ordered logistic regression was used to examine the relationship between ST2 levels and levels of AKI severity. RESULTS: Participants in this study showed a significant association between elevated preoperative ST2 levels and acute kidney risk. Before adjustment, the odds of patients developing AKIN stage 2 or 3, compared with AKIN stage 1, are 2.43 times higher (95% confidence interval, 1.86-3.16; P < .001) for patients in the highest tercile of preoperative ST2. After adjustment, patients in the highest tercile of preoperative ST2 had significantly greater odds of developing AKIN stage 2 or 3 AKI (odds ratio, 1.99; 95% confidence interval, 1.50-2.65; P < .001) compared with patients with AKIN stage 1. CONCLUSIONS: Preoperative ST2 levels are associated with postoperative AKI risk and can be used to identify patients at higher risk of developing AKI after cardiac surgery.

An Exploration of Shift Work, Fatigue, and Gender Among Police Officers: The BCOPS Study.

The present study examined the association between shift work and fatigue among male ( n = 230) and female ( n = 78) police officers. A 15-year work history database was used to define dominant shifts as day, afternoon, or night. A 10-item questionnaire created from the Standard Shiftwork Index (SSI) assessed fatigue. Gender-stratified analyses of variance and covariance and Poisson regression were used to compare means and prevalence of individual items across shifts. No significant differences in total fatigue scores were observed across shifts. However, the prevalence of the fatigue item "feelings of tiredness" was 89% higher among male officers working the afternoon shift compared with officers working the day shift (prevalence ratio [PR] = 1.89, 95% confidence interval [CI] = [1.12, 3.23], p = .020), after adjustment for covariates. Women reported a lower prevalence of tiredness than men on the afternoon shift. Organizations with afternoon shift workers should consider reducing fatigue at work through education and other methods.

The association between nonmedical use of prescription drugs and extreme weight control behavior among adolescents.

Although extreme weight control behavior (EWCB) is associated with substance use, no research has examined the association between the nonmedical use of prescription drugs (NMUPD) and EWCB. Self-report data were collected from a sample of 4,148 students in Grades 9-12 enrolled in 5 high schools across the United States. Logistic regression models were constructed to examine the nonmedical use of prescription pain relievers, depressants, stimulants, and a composite measure for any NMUPD, and the EWCB of fasting, use of diet pills, powders, or liquids, and vomiting or laxative use. Models were estimated before and after controlling for key covariates for males and females. Approximately 16% of respondents reported any EWCB during the past 30 days, while 11% reported any NMUPD during the past 30 days. After covariate adjustment, any NMUPD was associated with any EWCB in both males and females (p < .05), and all EWCB remained significant in females who reported prescription pain reliever use (p < .01), with 2 out of 3 remaining significant for prescription stimulant and depressant use (p < .01). The only significant association detected for males was between prescription pain reliever use and using diet pills, powders, or liquids (OR = 2.2, p < .01). Results suggest significant associations between NMUPD and EWCB, with variations by sex. These findings provide directions for additional research and point to several potential identification and intervention efforts. (PsycINFO Database Record

Association Between Discrimination and Objective and Subjective Sleep Measures in the Midlife in the United States Study Adult Sample.

OBJECTIVE: Evidence suggests that sleep quality is worse in nonwhite minorities compared with whites. Poor sleep is associated with higher levels of perceived interpersonal discrimination, which is consistently reported among minorities. However, the literature is limited in exploring discrimination with both objective and subjective sleep outcomes in the same sample. We examined the relationship between discrimination and markers of subjective and objective sleep in a racially diverse sample. METHODS: The analytic sample included 441 participants of the Midlife in the United States II (MIDUS) study (M [SD] age, 46.6 [1.03]; female, 57.9%; male, 42.1%; nonwhite, 31.7%). Complete data were available for 361 participants. Sleep measures included the Pittsburgh Sleep Quality Index, sleep latency, wake after sleep onset, and sleep efficiency derived from 7-day actigraphy. Discrimination was measured with the Williams Everyday Discrimination Scale. Ordinary least squares and logistic regression models were used to assess the relationship between discrimination and the subjective and objective measures of sleep. RESULTS: After adjusting for covariates, respondents with higher discrimination scores were significantly more likely to experience poor sleep efficiency (odds ratio, 1.12; p = .005) and report poorer sleep quality (odds ratio, 1.09; p = .029) on the basis of the Pittsburgh Sleep Quality Index. Higher discrimination scores were also associated with longer wake after sleep onset (b = 0.032, p < .01) and more sleep difficulties (b = 0.049, p = .01). Discrimination attenuated all differences in the sleep measures between whites and nonwhites except for sleep efficiency. CONCLUSIONS: The findings support the model that discrimination acts as a stressor that can disrupt subjective and objective sleep. These results suggest that interpersonal discrimination explains some variance in worse sleep among nonwhites compared with whites.

An Evaluability Assessment of the West Virginia Physical Activity Plan, 2015: Lessons Learned for Other State Physical Activity Plans.

BACKGROUND: The US National Physical Activity Plan (NPAP) was released in 2009 as a national strategic plan to increase physical activity (PA). The NPAP emphasized implementing state and local PA programs. Dissemination of information about NPAP has been limited, however. COMMUNITY CONTEXT: West Virginia is a predominantly rural state with high rates of chronic diseases associated with physical inactivity. In 2015 an evaluability assessment (EA) of the West Virginia Physical Activity Plan (WVPAP) was conducted, and community stakeholders were invited to participate in updating the plan. METHODS: A good EA seeks stakeholder input, assists in identifying program areas that need improvement, and ensures that a full evaluation will produce useful information. Data for this EA were collected via national stakeholder interviews, document reviews, discussions among workgroups consisting of state and local stakeholders, and surveys to determine how well the WVPAP had been implemented. OUTCOME: The EA highlighted the need for WVPAP leaders to 1) establish a specific entity to implement local PA plans, 2) create sector-specific logic models to simplify the WVPAP for local stakeholders, 3) evaluate the PA plan's implementation frequently from the outset, 4) use quick and efficient engagement techniques with stakeholders when working with them to select strategies, tactics, and measurable outcomes, and 5) understand the elements necessary to implement, manage, and evaluate a good PA plan. INTERPRETATION: An EA process is recommended for other leaders of PA plans. Our project highlights the stakeholders' desire to simplify the WVPAP so that it can be set up as a locally driven process that engages communities in implementation.

Tobacco and Other Drug Use among Foster Care Adolescents in West Virginia.

OBJECTIVES: This study presents tobacco and other drug use prevalence data from a statewide health screening program of foster care (FC) children in West Virginia, and explores associations with demographic and placement variables. METHODS: Logistic regression analyses adjusted for age, sex, and body mass index were conducted to determine if placement type and geographic region were associated with tobacco and other drug use among FC adolescents screened in 2012-2013 by the Early Periodic Screening Diagnosis and Treatment (EPSDT), or HealthCheck WV. RESULTS: One-third of the 12-17 year-olds used tobacco and 24% used other drugs. Results from the logistic regression analyses showed that significant associations between tobacco and drug use and placement variables persisted after controlling for covariates. Adolescents in home placements were significantly less likely to use tobacco (AOR=0.294; 95% CI: 0.196-0.441) or drugs (AOR=0.269; 95%, CI: 0.164-0.443) than those in agency placements. Details of significant regional variations also are presented. CONCLUSIONS: This study provides evidence of tobacco and drug use in West Virginia's FC adolescents and highlights a need for appropriate interventions for this vulnerable population.

Perceptions of the Role of West Virginia's Cooperative Extension Service in Tobacco Control Coalitions.

Despite the fact that the consequences of tobacco use are well identified and known, it remains the single most preventable cause of disease and death in the United States. In West Virginia alone, the adult prevalence of cigarette smoking is 26.8%. This study researches the perceptions of the Cooperative Extension Service's involvement and role in county-level coalitions that address tobacco use in West Virginia. The research findings provide practical areas to increase the role of the Extension Service in these vital efforts to save lives, reduce economic hardships on families, and reduce the health-care burden on the state government.

A Differential Item Functional Analysis by Age of Perceived Interpersonal Discrimination in a Multi-racial/ethnic Sample of Adults.

We investigated whether individual items on the nine item William's Perceived Everyday Discrimination Scale (EDS) functioned differently by age (<45 vs ≥ 45) within five racial groups in the United States: Asians (n=2,017); Hispanics (n=2,688); Black Caribbeans (n=1,377); African Americans (n=3,434); and Whites (n=854). We used data from the 2001-2003 National Survey of American Lives and the 2001-2003 National Latino and Asian Studies. Multiple-indicator, multiple-cause models (MIMIC) were used to examine differential item functioning (DIF) on the EDS by age within each racial/ethnic group. Overall, Asian and Hispanic respondents reported less discrimination than Whites; on the other hand, African Americans and Black Caribbeans reported more discrimination than Whites. Regardless of race/ethnicity, the younger respondents (aged <45 years) reported less discrimination than the older respondents (aged ≥ 45 years). In terms of age by race/ethnicity, the results were mixed for 19 out of 45 tests of DIF (40%). No differences in item function were observed among Black Caribbeans. "Being called names or insulted" and others acting as "if they are afraid" of the respondents were the only two items that did not exhibit differential item functioning by age across all racial/ethnic groups. Overall, our findings suggest that the EDS scale should be used with caution in multi-age multi-racial/ethnic samples.

Specific domains of Aß facilitate aggregation on and association with lipid bilayers.

A hallmark of Alzheimer's disease, a late-onset neurodegenerative disease, is the deposition of neuritic amyloid plaques composed of aggregated forms of the ß-amyloid peptide (Aß). Aß forms a variety of nanoscale, toxic aggregate species ranging from small oligomers to fibrils. Aß and many of its aggregate forms strongly interact with lipid membranes, which may represent an important step in several toxic mechanisms. Understanding the role that specific regions of Aß play in regulating its aggregation and interaction with lipid membranes may provide insights into the fundamental interaction between Aß and cellular surfaces. We investigated the interaction and aggregation of several Aß fragments (Aß1-11, Aß1-28, Aß10-26, Aß12-24, Aß16-22, Aß22-35, and Aß1-40) in the presence of supported model total brain lipid extract (TBLE) bilayers. These fragments represent a variety of chemically unique domains within Aß, that is, the extracellular domain, the central hydrophobic core, and the transmembrane domain. Using scanning probe techniques, we elucidated aggregate morphologies for these different Aß fragments in free solution and in the presence of TBLE bilayers. These fragments formed a variety of oligomeric and fibrillar aggregates under free solution conditions. Exposure to TBLE bilayers resulted in distinct aggregate morphologies compared to free solution and changes in bilayer stability dependent on the Aß sequence. Aß10-26, Aß16-22, Aß22-35, and Aß1-40 aggregated into a variety of distinct fibrillar aggregates and disrupted the bilayer structure, resulting in altered mechanical properties of the bilayer. Aß1-11, Aß1-28, and Aß12-24 had minimal interaction with lipid membranes, forming only sparse oligomers.