Relationship between efficacy and preferential targeting of soluble Aβ aggregates.

ABSTRACT:

Introduction

Amyloid beta (Aβ)-directed antibodies have shown varying degrees of efficacy against Alzheimer's disease (AD). This study explored the relationship between targeting of Aβ molecular species and therapeutic efficacy/adverse effects.

Methods

Surface plasmon resonance was used to measure binding of various Aβ-directed antibodies to monomers and soluble oligomers from AD brains. Plaque reactivity was assessed by immunohistochemistry and immunofluorescence. Antibody PMN310 was tested in AD mouse models.

Results

Pan-Aβ reactive antibodies that failed in the clinic lost the ability to bind AD brain oligomers when competing with monomers. Lecanemab, aducanumab, and donanemab, which slowed cognitive decline, and early stage PMN310 and ACU193 showed a greater abili

SUBMITTER: Kaplan JM 

PROVIDER: S-EPMC12662182 | biostudies-literature | 2025 Oct-Dec

REPOSITORIES: biostudies-literature