Targeting isoaspartate-modified Aβ rescues behavioral deficits in transgenic mice with Alzheimer's disease-like pathology.

ABSTRACT:

Background

Amyloid β (Aβ)-directed immunotherapy has shown promising results in preclinical and early clinical Alzheimer's disease (AD) trials, but successful translation to late clinics has failed so far. Compelling evidence suggests that post-translationally modified Aβ peptides might play a decisive role in onset and progression of AD and first clinical trials targeting such Aβ variants have been initiated. Modified Aβ represents a small fraction of deposited material in plaques compared to pan-Aβ epitopes, opening up pathways for tailored approaches of immunotherapy. Here, we generated the first monoclonal antibodies that recognize L-isoaspartate-modified Aβ (isoD7-Aβ) and tested a lead antibody molecule in 5xFAD mice.

Methods

This work comprises a combination of chemica

SUBMITTER: Gnoth K 

PROVIDER: S-EPMC7666770 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature