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.

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