Immunocytochemistry of LRRK2 in PD. Four antibodies raised against sequences corresponding to various regions shown on the schematic diagram of LRRK2 (red bars) were used on brainstem sections of PD (A-H) and age-matched controls (I-L). Intense immunolabeling of brainstem LBs in cases of PD was seen with Ab1 against LRRK2900–100 (A) and Ab4 against LRRK22500–2527(D). Both rim (A and D) and core (inset in D) of LBs were recognized. In contrast, LBs were not labelled in any case using antibodies directed against LRRK21246–1265 (Ab2, B) or LRRK21838–2133 (Ab3, C), for which the antigenic sites are located within the folded domains. The cell bodies of both pigmented and no-pigmented neurons (arrows) as well as axons (arrowheads) contain LRRK2, seen only using antibodies against sites outside the folded domains (Ab1, E and Ab4, H). In contrast, Ab4 staining was much less intense in control tissue (L). The muscle layer of both large and small vessels was consistently found to contain high levels of LRRK2 in almost all PD cases (seen in E, G, and H) and strikingly the vessels are the only structure immunolabeled with Ab3 recognizing LRRK21838–2133 in all cases studied (G and K). Ab2 to LRRK21246–1265 did not recognize LBs, cell bodies or vessels in any case (B, F, and J). Scale bars: A-D and inset = 10 μm; E-L = 100 μm.