Amyloid-β-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-beta oligomer-activated microglia into the striatum of na & iuml;ve 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-beta oligomer-triggered proteinopathies but also a novel animal model recapitulating the salient features of Alzheimer's disease. Amyloid plaques precede neurofibrillary tangles and Lewy bodies in Alzheimer's disease, but the relationship between these proteinopathies is unclear. Lee et al. show in mice that microglia activated by A beta drive neuroinflammation, which subsequently induces tau and alpha-synuclein aggregation and the associated neurodegenerative phenotypes.