Amyloid-ß-activated microglia can induce compound proteinopathies.
Brain
; 2024 Aug 28.
Article
em En
| MEDLINE
| ID: mdl-39194073
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-ß 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-ß oligomer-triggered proteinopathies but also a novel animal model recapitulating the salient features of Alzheimer's disease.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article