Amyloid-β-activated microglia can induce compound proteinopathies

Area of Science:

• Neuroscience
• Neuropathology
• Immunology

Background:

• Alzheimer's disease (AD) involves amyloid plaques, neurofibrillary tangles, and Lewy bodies.
• The interconnection between these proteinopathies remains unclear.

Purpose of the Study:

• To investigate the role of microglia-activated by amyloid-β oligomers in AD pathogenesis.
• To establish a novel animal model for AD with mixed pathologies.

Main Methods:

• Transplantation of amyloid-β oligomer-activated microglia into mouse striatum.
• Evaluation of neuropathological hallmarks, neuroinflammation, and cognitive/motor functions.
• Intervention using microglia depletion and anti-inflammatory drugs.

Main Results:

• Transplanted microglia induced AD features: tauopathy, synucleinopathy, gliosis, neuroinflammation, synapse loss, neuronal death, and functional deficits.
• Microglia depletion and anti-inflammatory treatment reversed these pathological changes.
• Demonstrated microglia-driven inflammation's critical role in mixed pathology development.

Conclusions:

• Microglia-activated by amyloid-β oligomers are sufficient to induce a comprehensive Alzheimer's-like disease model.
• This study elucidates mechanisms of amyloid-β oligomer-triggered proteinopathies.
• Highlights the therapeutic potential of targeting microglia-driven inflammation in AD.