Association of Peroxiredoxin IV with α-synuclein in Neuronal ER Indicates Lewy Bodies Are Seeded within ER in Parkinson's Disease and Dementia with Lewy Bodies.

hydrogen peroxide and is reported to be confined to endoplasmic reticulum (ER) in cultured cell lines. Methods & Results: Using human brain tissue from control, Parkinson's disease (PD), and dementia with Lewy bodies (DLB) cases we showed that peroxiredoxin IV is a 26kD protein under reducing conditions in gray and white matter. Using confocal immunohistochemistry, it is most abundant in neurons with lower levels in oligodendrocytes. Peroxiredoxin IV was detected in some microglia that may be due to phagocytosis of neuronal tissue, but it was not detected in astrocytes. Peroxiredoxin IV co-localized with the ER marker Sar1 indicating that it is confined to the ER. Co-localization of peroxiredoxin IV with α-synuclein in PD substantia nigra and DLB cortex indicated that α-synuclein aggregation was seeded within ER and that mature Lewy bodies were closely associated with the ER. In PD there was a more complex interaction between ER, α-synuclein and the DNA dye dapi suggesting some nuclear degradation in PD. Conclusion: These results show that peroxiredoxin IV is primarily a neuronal protein that is confined to ER. In addition, we show that α-synuclein aggregation and Lewy body development is seeded within ER.