Maintenance of neuronal TDP-43 expression requires axonal lysosome transport.

TDP-43 mislocalization and pathology occurs across a range of neurodegenerative diseases, but the pathways that modulate TDP-43 in neurons are not well understood. We generated a Halo-TDP-43 knock-in iPSC line and performed a genome-wide CRISPR interference FACS-based screen to identify modifiers of TDP-43 levels in neurons. A meta-analysis of our screen and publicly available screens identified both specific hits and pathways present across multiple screens, the latter likely responsible for generic protein level maintenance.

Triglyceride metabolism controls inflammation and -associated disease states in microglia.

Microglia modulate their cell state in response to various stimuli. Changes to cellular lipids often accompany shifts in microglial cell state, but the functional significance of these metabolic changes remains poorly understood. In human induced pluripotent stem cell-derived microglia, we observed that both extrinsic activation (by lipopolysaccharide treatment) and intrinsic triggers (the Alzheimer's disease-associated genotype) result in accumulation of triglyceride-rich lipid droplets.

The potential of digital health interventions to address health system challenges in Southeast Asia: A scoping review.

Objective: The World Health Organization (WHO) Southeast Asian region, comprising a quarter of the global population, faces significant healthcare challenges influenced by diverse economic and social conditions. The objective of this study is to map the Digital Health Intervention (DHI) functionalities across the nine axes of the healthcare system challenges (HSCs) model; we use WHO's DHIs classification framework and the Health System Challenges model. Our study findings help identify the gaps in the potential of the existing DHIs in addressing health system challenges in low- and middle-income countries.

Interprofessional education and collaborative practice with practicing radiographers: A mixed methods scoping review.

Introduction: There is increasing evidence substantiating the advantages of Interprofessional Education and Collaborative Practice (IPECP) in healthcare. Despite this, global adoption is still in its infancy. Whilst there has been some recognition of the importance of collaborative practice in healthcare, implementation of IPECP programs remain limited in many countries.

INTERCEPT-AD, a phase 1 study of intravenous sabirnetug in participants with mild cognitive impairment or mild dementia due to Alzheimer's disease.

Background: Soluble species of multimeric amyloid-beta including globular amyloid-beta oligomers (AβOs) and linear amyloid-beta protofibrils are toxic to neurons. Sabirnetug (ACU193) is a humanized monoclonal antibody, raised against globular species of soluble AβO, that has over 650-fold greater binding affinity for AβOs over monomers and appears to have relatively little binding to amyloid plaque.

Objectives: To assess safety, pharmacokinetics, and exploratory measures including target engagement, biomarker effects, and clinical efficacy of sabirnetug in participants with early symptomatic Alzheimer's disease (AD; defined as mild cognitive impairment and mild dementia due to AD).