Generation and Study of Antibodies against Two Triangular Trimers Derived from Aβ

Area of Science:

• Neuroscience
• Immunology
• Biochemistry

Background:

• Monoclonal antibodies (mAbs) targeting amyloid-beta (Aβ) are crucial for Alzheimer's disease (AD) research and therapy.
• Conformation-specific mAbs targeting oligomeric and fibrillar Aβ assemblies are of significant interest due to their role in AD pathogenesis.

Purpose of the Study:

• To generate novel rabbit monoclonal antibodies (mAbs) against structurally defined Aβ triangular trimers.
• To characterize these mAbs for selectivity, immunoreactivity with aggregated Aβ42, and efficacy in an AD mouse model.

Main Methods:

• Generation of rabbit mAbs using single B-cell sorting from immunized rabbits.
• Characterization of mAb selectivity for Aβ triangular trimers.
• Assessment of mAb immunoreactivity against aggregated Aβ42 and in 5xFAD mouse brain tissue.

Main Results:

• Successful generation of rabbit mAbs against known structures of Aβ oligomer mimics.
• Demonstrated selectivity of the generated mAbs for triangular trimers.
• Confirmed immunoreactivity of mAbs with aggregated Aβ42 and in AD mouse model brain tissue.

Conclusions:

• The developed mAbs provide valuable tools for studying antibody-amyloid recognition.
• These antibodies may advance the development of Alzheimer's disease diagnostics and immunotherapies.
• This work offers insights into targeting specific Aβ conformations for therapeutic strategies.