The Aβ protofibril selective antibody mAb158 prevents accumulation of Aβ in astrocytes and rescues neurons from Aβ-induced cell death.

ABSTRACT:

Background

Currently, several amyloid beta (Aβ) antibodies, including the protofibril selective antibody BAN2401, are in clinical trials. The murine version of BAN2401, mAb158, has previously been shown to lower the levels of pathogenic Aβ and prevent Aβ deposition in animal models of Alzheimer's disease (AD). However, the cellular mechanisms of the antibody's action remain unknown. We have recently shown that astrocytes effectively engulf Aβ₄₂ protofibrils, but store rather than degrade the ingested Aβ aggregates. In a co-culture set-up, the incomplete degradation of Aβ₄₂ protofibrils by astrocytes results in increased neuronal cell death, due to the release of extracellular vesicles, containing N-truncated, neurotoxic Aβ.

Methods

The aim of the presen

SUBMITTER: Sollvander S 

PROVIDER: S-EPMC5875007 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature