Antibody-based therapy and diagnosis for Alzheimer´s disease

Time period:

1 January 2026 – 31 December 2029

Project leader:

Dag Sehlin

Funder:

Swedish Research Council

Type of award:

Project grant

Total funding:

5,400,000 SEK

This project will study Alzheimer’s disease (AD) immunotherapy based on the amyloid-β (Aβ) antibody drug lecanemab. Aiming to improve its efficacy, safety, and precision, we will use the bispecific antibody bi-lecanemab, engineered for enhanced brain delivery, to study molecular and cellular therapeutic mechanisms in vitro and in vivo. Additionally, we will develop a PET method to visualize the same Aβ structures targeted by lecanemab.Using advanced microscopy, cell sorting-assisted transcriptomics, and PET imaging, we will study three interdependent aspects related to bi-lecanemab theranostics in human cell models and mouse models of Aβ pathology:Antibody brain entry and interactions with AβAntibody interactions with brain cells, focusing on phagocytosis of Aβ-antibody complexesDevelopment of a companion diagnostic PET ligand based on bi-lecanemab, for in vivo quantification of Aβ aggregatesThis four-year project will be led by the applicant and conducted at the Department of Public Health, UU, with national and international collaborators, using imaging and transcriptomics core facilities available at UU.Immunotherapy is the first disease-modifying AD treatment, but therapeutic mechanisms are difficult to study in humans and thus poorly understood. With a better mechanistic understanding of Aβ immunotherapy, leveraging an innovative strategy for antibody brain delivery, we can enhance the efficacy, safety, and precision of AD therapy.