Developing Topics.

Background: Sabirnetug (ACU193) is a humanized monoclonal antibody targeting soluble amyloid beta (Aβ) oligomers, which are early contributors to the pathogenesis of Alzheimer's Disease (AD). An ultrasensitive assay was developed to measure sabirnetug pharmacokinetics (PK) in CSF of individuals with early AD in the Phase 1 study INTERCEPT-AD (NCT04931459).

Method: The immunoassay was developed on the Meso Scale Diagnostics (MSD) S-PLEX with improved sensitivity through TURBO-TAG® technology.

Developing Topics.

Background: Sabirnetug (ACU193) is a humanized IgG2 antibody targeting soluble, synaptotoxic amyloid β oligomers (AβOs). AβOs accumulate in Alzheimer's disease (AD) and induce pre- and post-synaptic changes, resulting in dendritic spine loss, neuronal degeneration, and release of synaptic proteins into the CSF. Recently, we reported that three administrations of sabirnetug in an early AD population (INTERCEPT-AD Phase 1 study, NCT04931459) significantly lowered CSF levels of the post-synaptic protein neurogranin as well as pTau181.

Fecal deoxycholic acid associates with diet, intestinal microbes, and total bilirubin in primary sclerosing cholangitis.

Background & Aims: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with a strong association with inflammatory bowel disease and variable disease progression. We aimed to gain insights into the role of fecal bile acids (BA) on disease progression by determining the relationships between fecal BA, diet, and gut microbes, with markers of disease progression, BA synthesis, and farnesoid X receptor (FXR) activity.

Methods: BA levels in serum and stool, dietary intake, and markers of BA synthesis, and FXR activity were measured in 26 patients with early stage, large duct PSC.

The impact of interventions for depression on self-perceptions in young people: A systematic review & meta-analysis.

Negative self-perceptions are implicated in the development and maintenance of depression in young people, but little is known about their receptiveness to change in response to treatment. This paper reports on a pre-registered meta-analysis examining the extent to which treatments for depression in young people aged 11-24 result in changes to self-perceptions. Controlled treatment trials examining outcomes related to self-perceptions were synthesised (k = 20, N = 2041), finding small reductions in both symptoms of depression (g = -0.