Combining plasma Aβ and p-tau217 improves detection of brain amyloid in non-demented elderly.

Background: Maximizing the efficiency to screen amyloid-positive individuals in asymptomatic and non-demented aged population using blood-based biomarkers is essential for future success of clinical trials in the early stage of Alzheimer's disease (AD). In this study, we elucidate the utility of combination of plasma amyloid-β (Aβ)-related biomarkers and tau phosphorylated at threonine 217 (p-tau217) to predict abnormal Aβ-positron emission tomography (PET) in the preclinical and prodromal AD.

Methods: We designed the cross-sectional study including two ethnically distinct cohorts, the Japanese trial-ready cohort for preclinica and prodromal AD (J-TRC) and the Swedish BioFINDER study.

Uptake and Use of Care Companion, a Web-Based Information Resource for Supporting Informal Carers of Older People: Mixed Methods Study.

Background: Informal carers play a major role in supporting relatives and friends who are sick, disabled, or frail. Access to information, guidance, and support that are relevant to the lives and circumstances of carers is critical to carers feeling supported in their role. When unmet, this need is known to adversely affect carer resilience and well-being.

Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer's disease.

Blood biomarkers indicating elevated amyloid-β (Aβ) pathology in preclinical Alzheimer's disease are needed to facilitate the initial screening process of participants in disease-modifying trials. Previous biofluid data suggest that phosphorylated tau231 (p-tau231) could indicate incipient Aβ pathology, but a comprehensive comparison with other putative blood biomarkers is lacking. In the ALFA+ cohort, all tested plasma biomarkers (p-tau181, p-tau217, p-tau231, GFAP, NfL and Aβ42/40) were significantly changed in preclinical Alzheimer's disease.

Instructional and Assessment Redesign of a Sterile Compounding Course Using Immersive Simulation.

To revise a traditional sterile compounding course to include content, competencies, and immersive simulations relevant to the current practice of sterile compounding pharmacy. Faculty and staff at the University of North Texas System College of Pharmacy made significant revisions to an existing sterile compounding course. Instruction was provided in didactic and laboratory sessions and delivered in three modules: fundamental skills, integration of skills and knowledge, and exceptions and specialty topics.

Improving Trauma Care in Africa.

Bringing the first Advanced Trauma Care for Nurses (ATCN) provider and instructor courses to Zimbabwe was the initial step in an educational partnership spanning more than 8,000 miles. Zimbabwe is a South African country with limited health care services, severe financial restraints, and a shortage of health care professionals. All of these barriers made our goal of bringing an organized and systematic approach to trauma care even more important.

The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans.

BACE1 is a key protease controlling the formation of amyloid β, a peptide hypothesized to play a significant role in the pathogenesis of Alzheimer's disease (AD). Therefore, the development of potent and selective inhibitors of BACE1 has been a focus of many drug discovery efforts in academia and industry. Herein, we report the nonclinical and early clinical development of LY2886721, a BACE1 active site inhibitor that reached phase 2 clinical trials in AD.

Up-regulation of astrocyte metabotropic glutamate receptor 5 by amyloid-β peptide.

The effects of amyloid-beta peptide (Aβ) on astrocyte responses to activation of mGlu5 receptors have been investigated using calcium imaging. Pre-incubation with Aβ1-40 peptide for up to 72 h produced a time- and concentration-dependent 2-4 fold enhancement in the magnitude of the intracellular calcium mobilization response to the group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG). In contrast, pre-treatment with Aβ1-40 did not alter the calcium responses induced by other G protein coupled- or ion channel-receptors.

Development of homogeneous 384-well high-throughput screening assays for Abeta1-40 and Abeta1-42 using AlphaScreen technology.

Amyloid beta (Abeta) peptides are the major constituent of amyloid plaques, one of the hallmark pathologies of Alzheimer's disease. Accurate and precise quantitation of these peptides in biological fluids is a critical component of Alzheimer's disease research. The current most established assay for analysis of Abeta peptides in preclinical research is enzyme-linked immunosorbent assay (ELISA), which, although sensitive and of proven utility, is a multistep, labor-intensive assay that is difficult to automate completely.