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Updated: Jun 15, 2025
Rapid Generation of Amyloid from Native Proteins In vitro
Published on: December 5, 2013
Amyloid-β-activated microglia can induce compound proteinopathies
Sang Hwan Lee1,2, Eun-Jin Bae1,2, Dayana Perez-Acuna1
1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
Abstract:
Neuropathological features of Alzheimer's disease include amyloid plaques, neurofibrillary tangles and Lewy bodies, with the former preceding the latter two. However, it is not fully understood how these compound proteinopathies are interconnected. Here, we show that transplantation of amyloid-β oligomer-activated microglia into the striatum of naïve mice was sufficient to generate all the features of Alzheimer's disease, including widespread tauopathy and synucleinopathy, gliosis, neuroinflammation, synapse loss, neuronal death, and cognitive and motor deficits. These pathological features were eliminated by microglia depletion and anti-inflammatory drug administration. Our results suggest the crucial roles of microglia-driven inflammation in development of mixed pathology. This study provides not only mechanistic insights into amyloid-β oligomer-triggered proteinopathies but also a novel animal model recapitulating the salient features of Alzheimer's disease.
Insights
Microglia activation by amyloid-β oligomers triggers Alzheimer's-like pathology, including tauopathy and synucleinopathy, in mice. This neuroinflammation drives mixed proteinopathies and cognitive deficits, highlighting microglia's central role.
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.
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