Passive immunotherapy for Alzheimer's disease.

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Alzheimer's disease (AD) is a leading cause of neurodegeneration with limited treatment options.
• Despite numerous past failures, recent advancements in passive immunotherapy offer new therapeutic avenues for AD.
• Key pathological hallmarks of AD include amyloid-beta (Aβ) plaques, tau tangles, and neuroinflammation.

Purpose of the Study:

• To review the characteristics, clinical trial data, and mechanisms of action of monoclonal antibodies (mAbs) for AD treatment.
• To evaluate the efficacy and side effects of anti-amyloid-beta (Aβ) mAbs, such as lecanemab and donanemab.
• To explore the therapeutic potential of mAbs targeting tau or neuroinflammation modulators in AD.

Main Methods:

• Review of clinical trial data for mAbs targeting Aβ, tau, and neuroinflammation.
• Analysis of mechanisms of action for various immunotherapy agents.
• Evaluation of efficacy and safety profiles from Phase III clinical trials.

Main Results:

• Lecanemab and donanemab demonstrated significant efficacy in improving cognition and clearing amyloid plaques in AD patients during Phase III trials.
• Factors influencing the efficacy and side effects of anti-Aβ mAbs were discussed.
• mAbs targeting mid-region or pathogenic tau, as well as inflammatory regulators, show therapeutic potential.

Conclusions:

• Passive immunotherapy targeting key players in AD pathogenesis represents a promising strategy for effective AD treatment.
• Monoclonal antibodies offer a viable approach to address cognitive decline and pathological hallmarks of Alzheimer's disease.
• Further research into tau-targeting and anti-inflammatory mAbs could yield additional treatment options for AD.