Do current therapeutic anti-Aβ antibodies for Alzheimer’s disease engage the target?

Reducing amyloid-β peptide (Aβ) burden at the pre-symptomatic stages of Alzheimer’s disease (AD) is currently the advocated clinical strategy for treating this disease. The most developed method for targeting Aβ is the use of monoclonal antibodies including bapineuzumab, solanezumab and crenezumab. We have synthesized these antibodies and used surface plasmon resonance (SPR) and mass spectrometry to characterize and compare the ability of these antibodies to target Aβ in transgenic mouse tissue as well as human AD tissue. SPR analysis showed that the antibodies were able to bind Aβ with high affinity. All of the antibodies were able to bind Aβ in mouse tissue. However, significant differences were observed in human brain tissue. While bapineuzumab was able to capture a variety of N-terminally truncated Aβ species, the Aβ detected using solanezumab was barely above detection limits while crenezumab did not detect any Aβ. None of the antibodies were able to detect any Aβ species in human blood. Immunoprecipitation experiments using plasma from AD subjects showed that both solanezumab and crenezumab have extensive cross-reactivity with non-Aβ related proteins. Bapineuzumab demonstrated target engagement with brain Aβ, consistent with published clinical data. Solanezumab and crenezumab did not, most likely as a result of a lack of specificity due to cross-reactivity with other proteins containing epitope overlap. This lack of target engagement raises questions as to whether solanezumab and crenezumab are suitable drug candidates for the preventative clinical trials for AD.     

Screening for Depression and High Utilization of Health Care Resources Among Patients in Primary Care

The study aims to evaluate the prevalence of depression and the severity of depressive symptoms among primary care patients, who are high utilizers (HU) of health care resources. A cross-sectional, two-stage design was applied to screen for depression using the Brief Psychiatric Health Questionnaire and the Diagnostic Expert System for Psychiatric Disorders. A total of 38 primary care physicians accredited to practice in Berlin and Potsdam in Germany participated in the study. A total of 1,775 patients participated, 507 were identified as HU, 182 (36 %) of these were depressed compared to 81 (11 %) of the typical utilizers (p < 0.001). The depression score was higher and acute suicidality was more prevalent in HU than in typical utilizers (p < 0.001). Our results suggest that HU represent a population with a high prevalence of depression in primary care and should be considered for routine depression screening.     

Emotion dysregulation as a maintenance factor of borderline personality disorder features

We examined within-individual changes in emotion dysregulation over the course of one year as a maintenance factor of borderline personality disorder (BPD) features. We evaluated the extent to which (1) BPD symptom severity at baseline predicted within-individual changes in emotion dysregulation and (2) within-individual changes in emotion dysregulation predicted four BPD features at 12-month follow-up: affective instability, identity disturbances, negative relationships, and impulsivity. The specificity of emotion dysregulation as a maintaining mechanism of BPD features was examined by controlling for a competing intervening variable, interpersonal conflict. BPD symptoms at baseline predicted overall level and increasing emotion dysregulation. Additionally, increasing emotion dysregulation predicted all four BPD features at 12-month follow-up after controlling for BPD symptoms at baseline. Further, overall level of emotion dysregulation mediated the association between BPD symptom severity at baseline and both affective instability and identity disturbance at 12-month follow-up, consistent with the notion of emotion dysregulation as a maintenance factor. Future research on the malleability of emotion dysregulation in laboratory paradigms and its effects on short-term changes in BPD features is needed to inform interventions.     

Stroke service: How can we improve and measure outcomes? Consensus summary from a global stroke forum

The success of acute stroke treatment is first and foremost time‐dependent, and the need for improvement in acute stroke management is demonstrated by the fact that only a minority of patients gain access to treatment – in particular, intravenous recombinant tissue plasminogen activator (IV tPA) – within the necessary time window. Standards of acute stroke care vary widely both regionally and nationally; consequently, various healthcare organizations have undertaken initiatives to measure and improve quality of care. To date, most quality measures have been process‐based, focusing primarily on metrics of patient care in the acute hospital‐based setting (e.g., time to recombinant tPA administration). Therefore, there remains a need for metrics designed to assess how improvements in process translate into patient outcomes. A global forum was convened to share best practice and provide consensus recommendations on core metrics for measuring improvements in access to care and patient outcomes. Recommendations for core metrics of patient outcomes include hospital‐based outcomes (e.g., neurological status at 24 h, ambulatory status at discharge) and post‐discharge outcomes (e.g., modified Rankin Scale score at 30 and/or 90 days). Recommendations for best practice relating to aspects of people, process, and technology involved in the stroke treatment pathway that may help provide improvements in these core outcome measures are also outlined.