Validation of a new model and therapy for Alzheimer´s disease

Purpose and goal

The aim of this project was to evaluate improved selection criteria for novel oligomer-specific therapeutics in Alzheimer’s disease. The antibody ALZ-201, with 100% amyloid-beta oligomer specificity, was evaluated in a transgenic mouse model of the disease and in a new model based on the effect patient brain extracts has on zebrafish. Results generated were supportive of the applicability of the new model but found that the mouse model is less well suited for addressing the issue at hand.

Expected results and effects

The effects of treatment of the mouse model were, as expected, minor. But one interesting effect was observed on a synapse protein that has been identified as central for oligomer toxicity by others. The zebrafish model also demonstrated that the form of amyloid-beta that is neutralised by ALZ-201 is indeed present in diseased brains but not in healthy control brains. Taken together, the project generated insights into how the selection of new therapeutics in Alzheimers can be improved.

Planned approach and implementation

Both parties in this project contributed their products and know-how to address the issue of how to best assess the potential efficacy of a novel oligomer-specific therapeutic for Alzheimer’s disease. Alzinova contributed the antibody ALZ-201 and the University of Gothenburg a novel disease model based on patient material. The results generated in this project demonstrate that models based on patient material are preferred to transgenic mouse models.