Passive immunization inhibits tau phosphorylation and improves recognition learning and memory in 3xTg-AD mice

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Tau pathology is a key driver in Alzheimer's disease (AD) and tauopathies.
• Tau immunotherapy presents a potential therapeutic strategy for these neurodegenerative conditions.

Purpose of the Study:

• To screen monoclonal antibodies targeting tau for therapeutic potential in AD.
• To evaluate the efficacy of antibody 77G7 in reducing tau pathology and improving cognitive function in AD mouse models.

Main Methods:

• Screening of four monoclonal antibodies (43D, 63B, 39E10, 77G7) targeting different tau epitopes.
• In vitro assessment of antibody-mediated tau clearance and neuronal cell entry.
• In vivo studies involving intra-cerebroventricular and intravenous injections of 77G7 in wild-type and 3xTg-AD mouse models.

Main Results:

• Antibody 77G7, targeting the microtubule-binding domain, promoted dose-dependent tau clearance in vitro.
• Intra-cerebroventricular injection of 77G7 reduced tau levels in wild-type mouse brains.
• Intravenous 77G7 administration decreased tau hyperphosphorylation and improved novel object recognition in 3xTg-AD mice, without affecting aggregated tau levels.

Conclusions:

• The epitope targeted by tau antibodies is critical for immunotherapy efficacy.
• Antibody 77G7 demonstrates potential for tau-directed immunotherapy in Alzheimer's disease and related tauopathies.