RESEARCH HIGHLIGHT - Prominent microglial inclusions in transgenic mouse models of α-synucleinopathy that are distinct from neuronal lesions

Accumulation of α-synuclein (α-syn) aggregates is a pathological hallmark of a group of neurodegenerative diseases called α-synucleinopathies. α-syn is the major component of Lewy bodies and Lewy neurites, which are intracellular inclusions found in neurons of patients with Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). α-syn also accumulates in oligodendrocytes to form glial cytoplasmic inclusions. 

The initial aim of the present work from the DZNE team was to study disease progression and features of α-syn lesions among TG mouse models of α-synucleinopathies and their correlation with αS conformers. The results presented in this paper published in Acta Neuropathologica Communication revealed major differences among the mouse lines in age-of-symptom onset and disease progression. Postmortem analysis though revealed an overall very similar appearance and distribution of the α-syn lesions in all the lines. However, strikingly, in addition to neuronal lesions, we found α-syn-positive inclusions in microglia in all four lines.

This unexpected finding of robust inclusions in microglia in α-syn TG mice suggests that there is a link between the neuronal and microglial inclusions in α-syn TG mice.

This project receives funding from the Innovative Medicines Initiative 2 Joint Undertaking ( under grant agreement No 116060. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.

This work is supported by the Swiss State Secretariat for Education‚ Research and Innovation (SERI) under contract number 17.00038.

The opinions expressed and arguments employed herein do not necessarily reflect the official views of these funding bodies.

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