Amyloid-Directed Antibodies: Past, Present, and Future

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Alzheimer's disease (AD) is a prevalent neurodegenerative disorder in individuals over 65, characterized by cognitive decline.
• Definitive AD diagnosis relies on postmortem detection of amyloid-beta (Aβ) plaques and tau tangles.
• While AD's exact cause remains unknown, immunotherapies are actively investigated for treatment, showing promise in reducing AD pathology and symptoms.

Purpose of the Study:

• To review and evaluate passive immunotherapies for Alzheimer's disease (AD) that demonstrate potential for development and clinical use.
• To identify promising immunotherapy candidates for AD treatment based on regulatory status and emerging research.

Main Methods:

• A narrative review approach was employed to select immunotherapies.
• Medications were chosen based on potential clinical effectiveness and regulatory standing (FDA accepted, fast-track, pending, or emerging).

Main Results:

• The review identified two fully FDA-approved anti-amyloid-beta (Aβ) monoclonal antibodies (mAbs).
• One mAb received FDA fast-track status, with two additional therapies on hold, three discontinued, and three promising emerging therapies identified.

Conclusions:

• Passive immunotherapies are anticipated to become a preferred, evidence-based treatment for AD with brain Aβ deposits, aiding symptom management and potentially slowing progression.
• Lecanemab and donanemab require further studies to optimize patient selection and safety profiles.
• These therapies represent a significant step towards disease-modifying treatments for early-stage AD patients with amyloid pathology.