Amyloid-ß-activated microglia can induce compound proteinopathies.

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.