Despite the beneficial effect of immunotherapy, recent experimental trials have reported amyloid-related imaging abnormalities (ARIA) rates of 41% in patients with Alzheimer’s disease (AD). This common adverse event, manifesting as brain edema or microhemorrhages, ranges in severity and can cause symptoms such as headache, confusion, and nausea. Mourad Tayebi, PhD, Western Sydney University, Penrith, Australia, talks about the importance of characterizing the molecular mechanisms underlying this process. They previously looked at mouse models of prion disease, noting ARIA-like behavior when infusing anti-prion antibodies into the brain that was associated with activation of neuronal allergenic proteomes. They therefore hypothesized that similar events may occur in patients with AD. To test this, anti-amyloid antibodies were added to human induced pluripotent stem cells-derived neurons co-cultured with microglia. They discovered that the antibodies led to allergenic-related protein expression, specifically a type 1 hypersensitivity reaction. There was a clear shift from an anti-inflammatory to a pro-inflammatory cytokine profile, exacerbated by the presence of microglia. While ongoing work in mouse models suggests that this type 1 hypersensitivity is histamine independent, Dr Tayebi and his team are still looking into the specific pathways involved. This study highlights the importance of in-depth characterization of therapeutic antibodies as part of the developmental process. This interview took place at the AD/PD™ 2023 congress in Gothenburg, Sweden.

These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.

свернуть