Background Inducing brain ATP-binding cassette 1 (ABCA1) activity in Alzheimer’s disease (AD) mouse models is associated with improvement in AD pathology. The purpose of this study was to investigate the effects of the ABCA1 agonist peptide CS-6253 on amyloid-β peptides (Aβ) and lipoproteins in plasma and cerebrospinal fluid (CSF) of cynomolgus monkeys, a species with amyloid and lipoprotein metabolism similar to humans. Methods CS-6253 peptide was injected intravenously into cynomolgus monkeys at various doses in three different studies. Plasma and CSF samples were collected at several time points before and after treatment. Levels of cholesterol, triglyceride (TG), lipoprotein particles, apolipoproteins, and Aβ were measured using ELISA, ion-mobility analysis, and asymmetric-flow field-flow fractionation (AF4). The relationship between the change in levels of these biomarkers was analyzed using multiple linear regression models and linear mixed-effects models. Results Following CS-6253 intravenous injection, within minutes, small plasma high-density lipoprotein (HDL) particles were increased. In two independent experiments, plasma TG, apolipoprotein E (apoE), and Aβ42/40 ratio were transiently increased following CS-6253 intravenous injection. This change was associated with a non-significant decrease in CSF Aβ42. Both plasma total cholesterol and HDL-cholesterol levels were reduced following treatment. AF4 fractionation revealed that CS-6253 treatment displaced apoE from HDL to intermediate-density- and low density-lipoprotein (IDL/LDL)-sized particles in plasma. In contrast to plasma, CS-6253 had no effect on the assessed CSF apolipoproteins or lipids. Conclusions Treatment with the ABCA1 agonist CS-6253 appears to favor Aβ clearance from the brain.

BackgroundDermatologists and other providers play essential roles in managing the dermatologic care of pediatric patients. This study aims to identify patterns and elucidate factors associated with receiving dermatologic care in the United States.MethodsThe National Ambulatory Medical Care Survey (NAMCS) was used to identify pediatric patients with dermatologic diagnoses from 2009 to 2015. Clinical and demographic information were evaluated, and visit diagnoses were stratified based on provider type (dermatologists vs. non‐dermatologists). Multivariate logistic regression analysis was used to identify key predictors of outpatient dermatology care for pediatric patients. National estimates of diagnoses were procured using weights provided within the NAMCS database to project disease incidence.ResultsA total of 85,217,557 pediatric patients (survey‐weighted) were observed during the study period. Of the sampled patients, 29.3% were evaluated by dermatologists, while 70.7% were seen by non‐dermatology providers. Atopic dermatitis was the most common diagnosis encountered by dermatologists in ages 0–3 years, while unspecified contact dermatitis was the most common diagnosis reported by non‐dermatologists in all age groups. On multivariable logistic regression, ≥1 year of age, Caucasian race, private insurance versus Medicaid, residence in a metropolitan area, referral from another provider, and longer appointment wait time were associated with an increased likelihood of being evaluated by a dermatologist compared to a non‐dermatologist.ConclusionsNon‐dermatologists are responsible for the majority of pediatric dermatologic care. For pediatric patients, health disparities by race, insurance status, and rurality present significant challenges to being evaluated by a dermatologist.