ABSTRACT
Parkinson’s disease (PD) is a progressive, neurodegenerative disorder characterised by the abnormal accumulation of α-synuclein (α-syn) aggregates. Central to disease progression is the gradual spread of pathological α-syn. α-syn aggregation is closely linked to progressive neuron loss. As such, clearance of α-syn aggregates may slow the progression of PD and lead to less severe symptoms. Evidence that non-neuronal cells play a role in PD and other synucleinopathies such as Lewy body dementia and multiple system atrophy are increasing. Our previous work has shown that pericytes — vascular mural cells that regulate the blood-brain barrier — contain α-syn aggregates in human PD brains. Here, we demonstrate that pericytes efficiently internalise fibrillar α-syn irrespective of being in a monoculture or mixed neuronal cell culture. Pericytes efficiently break down α-syn aggregates in vitro, with clear differences in the number of α-syn aggregates/cell and average aggregate size when comparing five pure α-syn strains (Fibrils, Ribbons, fibrils65, fibrils91 and fibrils110). Furthermore, pericytes derived from PD brains have a less uniform response than those derived from control brains. Our results highlight the vital role brain vasculature may play in reducing α-syn burden in PD.
Footnotes
Birger Victor Dieriks: v.dieriks{at}auckland.ac.nz, Blake Highet: b.highet{at}auckland.ac.nz, Ania Alik: ania.alik2{at}cea.fr, Tracy Bellande: tracy.bellande{at}cea.fr, Taylor Stevenson: t.stevenson{at}auckland.ac.nz, Victoria Low: v.low{at}auckland.ac.nz, Thomas Park: thomas.park{at}auckland.ac.nz, Jason Correia: JasonC{at}adhb.govt.nz, Patrick Schweder: PatrickS{at}adhb.govt.nz, Richard Faull: rlm.faull{at}auckland.ac.nz, Ronald Melki : ronald.melki{at}cnrs.fr, Maurice Curtis: m.curtis{at}auckland.ac.nz, Mike Dragunow: dragunow{at}auckland.ac.nz